FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tuan, RS AF Tuan, RS TI Cellular signaling in developmental chondrogenesis: N-cadherin, Wnts, and BMP-2 SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT 4th Symposium of the International-Cartilage-Repair-Society CY JUN 15-18, 2002 CL TORONTO, CANADA SP Int Cartilage Repair Soc ID LIMB MESENCHYMAL CHONDROGENESIS; BONE MORPHOGENETIC PROTEIN-2; IN-VITRO; EXPRESSION; CELLS; STIMULATION; INVOLVEMENT; BUD; DIFFERENTIATION; POLARITY C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bldg 50,Room 1503,MSC8022, Bethesda, MD 20892 USA. NR 26 TC 66 Z9 68 U1 0 U2 8 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PY 2003 VL 85A SU 2 BP 137 EP 141 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 665TN UT WOS:000182137500020 PM 12721357 ER PT J AU Tanaka, H Wakisaka, A Ogasa, H Kawai, S Liang, CT AF Tanaka, H Wakisaka, A Ogasa, H Kawai, S Liang, CT TI Effects of basic fibroblast growth factor on osteoblast-related gene expression in the process of medullary bone formation induced in rat femur SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Article DE basic fibroblast growth factor; gene expression; bone formation ID COLLAGEN MESSENGER-RNA; IN-VIVO; ALKALINE-PHOSPHATASE; LOCAL APPLICATION; OLD RATS; IGF-I; CELLS; STIMULATION; OSTEOPONTIN; FRACTURE AB The effects of basic fibroblast growth factor (bFGF) on osteogenic differentiation in-vivo were investigated using a rat bone marrow ablation model. bFGF was infused directly into rat femora for 6 days after bone marrow ablation. The contralateral femur was infused with vehicle only and used as control. Bone formation was induced in the rat femoral cavity, and the gene expression of osteoblast markers was examined. Treatment with bFGF at 50 and 100ng/day significantly enhanced the mRNA levels of osteopontin compared with the levels in the control leg, with increases of 25% and 24%, respectively. In contrast, bFGF infusion at 50 ng/day provoked a significant (nearly 20%) inhibition of expression for type I collagen. Infusion of bFGF at a higher dose exhibited an inhibitory tendency for bFGF action on gene expression. There were no significant changes in alkaline phosphatase and osteocalcin mRNA levels in response to any dose of bFGF. The findings presented here suggest that bFGF modulates osteogenic differentiation in-vivo and may play an important role in the process of bone remodeling. C1 Yamaguchi Univ, Sch Med, Dept Orthoped Surg, Ube, Yamaguchi 7558505, Japan. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Natl Hlth Res Inst, Taipei, Taiwan. RP Tanaka, H (reprint author), Yamaguchi Univ, Sch Med, Dept Orthoped Surg, 1-1-1 Minamikogushi, Ube, Yamaguchi 7558505, Japan. NR 34 TC 6 Z9 8 U1 0 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0914-8779 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PY 2003 VL 21 IS 2 BP 74 EP 79 DI 10.1007/s007740300012 PG 6 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 653AT UT WOS:000181413600003 PM 12601570 ER PT J AU Sierra-Galan, LM Ingkanisorn, WP Rhoads, KL Agyeman, KO Arai, AE AF Sierra-Galan, LM Ingkanisorn, WP Rhoads, KL Agyeman, KO Arai, AE TI Qualitative assessment of regional left ventricular function can predict MRI or radionuclide ejection fraction: An objective alternative to eyeball estimates SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE magnetic resonance imaging; regional wall motion abnormalities; left ventricular function; ejection fraction; ischemic heart disease; hyperkinetic; myocardial contraction ID CORONARY-ARTERY DISEASE; CARDIOVASCULAR MAGNETIC-RESONANCE; ACUTE MYOCARDIAL-INFARCTION; WALL-MOTION ANALYSIS; DOBUTAMINE STRESS; HEART-FAILURE; BYPASS-SURGERY; ECHOCARDIOGRAPHY; SURVIVAL; ACQUISITION AB Purpose. Assessment of left ventricular function is important in patients with heart disease. We hypothesized that regional wall motion assessed qualitatively by cine magnetic resonance imaging (MRI) can predict the left ventricular ejection fraction (EF). Methods. The correlations between MRI EF and the American Society of Echocardiography (ASE) score index and a modified ASE score index were established in 117 subjects. The model was tested in the next 86 patients. Interobserver variability was studied in 30 patients. Radionuclide EF was compared in 81 patients. Cine MRI studies were performed on a 1.5 T scanner. Results. From the initial 117 patients, there was a linear correlation between the ASE score index and MRI (r = 0.85), but the relationship improved by including a category of hyperkinetic wall motion (r = 0.90). Using these correlations to predict MRI EF in the next 86 patients, there was a good agreement (r = 0.93 for the ASE score index and r = 0.97 for the modified ASE score index). Correlations between radionuclide EF and the EF predicted by the modified ASE score index or the MRI EF by planimetry were similar (r = 0.91 vs. r = 0.90, respectively). Four observers tested the model and achieved comparable results (r = 0.88 to 0.95). Conclusions. There is a close relationship between ejection fraction and the ASE score index or modified ASE score index. This correlation can provide an objective prediction of ejection fraction based solely on a qualitative reading of regional wall thickening. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,B1D61,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. NR 54 TC 9 Z9 9 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2003 VL 5 IS 3 BP 451 EP 463 DI 10.1081/JCMR-120022261 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 700EH UT WOS:000184099300004 PM 12882076 ER PT J AU Sorger, JM Wyman, BT Faris, OP Hunter, WC McVeigh, ER AF Sorger, JM Wyman, BT Faris, OP Hunter, WC McVeigh, ER TI Torsion of the left ventricle during pacing with MRI tagging SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE cardiac; MRI; pacing; torsion; ventricle ID CANINE LEFT-VENTRICLE; ROTATIONAL DEFORMATION; MECHANICAL ACTIVATION; PACED HEART; RELAXATION; HUMANS; IMAGES; PHASE; TWIST; CATECHOLAMINES AB The effects of different pacing protocols on left ventricular (LV) torsion were evaluated over the full cardiac cycle. A systolic and diastolic series of magnetic resonance imaging (MRI) scans were combined and used to calculate the torsion of the LV in a canine model. The asynchronous activation resulting from ventricular pacing interferes with the temporal evolution of LV torsion. The torsion of the left ventricle was investigated under three different protocols: 1) right atrial pacing, 2) right ventricular pacing, and 3) simultaneous pacing from the right ventricular apex and LV base. The temporal evolution of torsion was determined from tagged MRI and evaluated over the cardiac cycle. The peak rotation for the atrially paced hearts was 11.1degrees (+/-3.5degrees) compared to 6.1degrees (+/-1.7degrees) and 6.1degrees (+/-0.7degrees) for those hearts paced from the right ventricle and from both ventricles, respectively. While biventricular pacing increases the synchrony of contraction, it significantly alters the pattern of LV torsion. From these experiments we have shown that measuring torsion is an extremely sensitive indicator of the existence of ectopic excitation. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. RP McVeigh, ER (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,10 Ctr Dr,MSC-1061,Room B1D416, Bethesda, MD 20892 USA. EM emcveigh@bme.jhu.edu FU Intramural NIH HHS [Z01 HL004608-08]; NHLBI NIH HHS [HL45683] NR 33 TC 37 Z9 42 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2003 VL 5 IS 4 BP 521 EP 530 DI 10.1081/JCMR-120025227 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 745BX UT WOS:000186669400001 PM 14664130 ER PT J AU Pai, VM Wen, H AF Pai, VM Wen, H TI Rapid-motion-perception based cardiac navigators: Using the high flow blood volume as a marker for the position of the heart SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE navigators; MRI; cardiac tracking; complex difference; blood flow; slice-tracking; motion ID RESONANCE CORONARY ANGIOGRAPHY; MR-ANGIOGRAPHY; RESPIRATORY MOTION; BREATH-HOLD; ARTERIES; REDUCTION; AGREEMENT AB Navigators have been developed as one of the many approaches to reducing motion artifacts due to respiration. A typical navigator approach applies a pencil-beam style profile crossing the diaphragm to track the superior-inferior (SI) motion of the diaphragm, and subsequently applying correlations to determine the heart location. This approach necessitates a priori knowledge of the correlation coefficients between heart and diaphragm motion, a variable parameter among patients. This paper presents an alternative navigator method based on Rapid Motion Perception (RaMP). This method acquires profiles of the ventricular blood volume based on its high flow velocity. The position of the blood volume is a direct representation of the position of the heart. This method allows cardiac navigation in two orthogonal directions simultaneously, eliminates the need to obtain correlations to the diaphragm motion, and increases tracking reliability for individual patients. A prospective version of RaMP navigators has been implemented on a clinical 1.5 T scanner, and preliminary tests on human volunteers show that this method can successfully track the heart position over the entire respiratory period. This navigation scheme is tested for predicting superior-inferior and anterior-posterior (AP) motion of the heart for breath-hold and free breathing conditions. Bland-Altman plots comparing the motion predicted by the navigators and that computed from single-shot images immediately following the navigators, show that the accuracy of this method is +/- 1.43 mm in the SI direction and +/- 0.84 mm in the AP direction. The RaMP navigator is suited for real-time tracking of the bulk translational motion of the heart. C1 NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Pai, VM (reprint author), NYU, Sch Med, Dept Radiol, 650 1st Ave,Room 611, New York, NY 10016 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [ZIA HL004606-13] NR 25 TC 0 Z9 0 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2003 VL 5 IS 4 BP 531 EP 543 DI 10.1081/JCMR-120025228 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 745BX UT WOS:000186669400002 PM 14664131 ER PT J AU Liu, Y Rao, MS AF Liu, Y Rao, MS TI Transdifferentiation - Fact or artifact SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE fate; competence; dedifferentiation; siRNA; methylation; heterochromatin; senescence; lateral inhibition ID TUBE CELLS DIFFERENTIATE; ADULT STEM-CELLS; BONE-MARROW; NEURAL CREST; PROGENITOR CELLS; GENE-EXPRESSION; MOUSE BRAINS; IN-VIVO; NEURONS; MULTIPOTENT AB Normal development appears to involve a progressive restriction in developmental potential. However, recent evidence suggests that this progressive restriction is not irreversible and can be altered to reveal novel phenotypic potentials of stem, progenitor, and even differentiated cells. While some of these results can be explained by the presence of contaminating cell populations, persistence of pluripotent stem cells, cell fusion, etc., several examples exist that are difficult to explain as anything other than "true transdifferentiation" and/or dedifferentiation. These examples of transdifferentiation are best explained by understanding how the normal process of progressive cell fate restriction occurs during development. We suggest that subversion of epigenetic controls regulating cell type specific gene expression likely underlies the process of transdifferentiation and it may be possible to identify specific factors to control the transdifferentiation process. We predict, however, that transdifferentiation will not be reliable or reproducible and will probably require complex manipulations. Published 2002 Wiley-Liss, Inc.(dagger) C1 NIA, Lab Neurosci, Baltimore, MD 21224 USA. Univ Utah, Sch Med, Dept Anat & Neurobiol, Salt Lake City, UT 84132 USA. RP Rao, MS (reprint author), NIA, Lab Neurosci, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 67 TC 82 Z9 89 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 1 PY 2003 VL 88 IS 1 BP 29 EP 40 DI 10.1002/jcb.10281 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 629BC UT WOS:000180029700007 PM 12461772 ER PT J AU Poroikov, VV Filimonov, DA Ihlenfeldt, WD Gloriozova, TA Lagunin, AA Borodina, YV Stepanchikova, AV Nicklaus, MC AF Poroikov, VV Filimonov, DA Ihlenfeldt, WD Gloriozova, TA Lagunin, AA Borodina, YV Stepanchikova, AV Nicklaus, MC TI PASS biological activity spectrum predictions in the Enhanced open NCI Database Browser SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID DRUG INFORMATION-SYSTEM; SUBSTANCES AB The application of the program PASS (Prediction of Activity Spectra for Substances) to about 250 000 compounds of the NCI Open Database and the incorporation of over 64 million PASS predictions in the Enhanced NCI Database Browser are described. A total of 565 different types of activity are included, encompassing general pharmacological effects, specific mechanisms of action. known toxicities. and others. Application of this Web-based service to prediction of activities of the kinds "Angiogenesis inhibitor." "Antiviral (HIV)", and a set of activities that can be associated with antineoplastic action are reported. For this latter data set, a very substantial enrichment over random selection was found in the PASS predictions. It is shown how the user can conduct complex searches by combining ranges of PASS-predicted probabilities of compounds to be active or to be inactive. respectively, with, e.g., value ranges of physicochemical parameters, presence or absence of particular substructural fragment, and other search criteria. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH,NCI Frederick, Frederick, MD 21702 USA. Russian Acad Med Sci, VN Orekhovich Inst Biomed Chem, Lab Struct Funct Based Drug Design, Moscow 119121, Russia. Univ Erlangen Nurnberg, Inst Organ Chem, D-91052 Erlangen, Germany. Univ Erlangen Nurnberg, Comp Chem Ctr, D-91052 Erlangen, Germany. RP Nicklaus, MC (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH,NCI Frederick, 376 Boyles St, Frederick, MD 21702 USA. RI Poroikov, Vladimir/O-2769-2013; Nicklaus, Marc/N-4183-2014; Lagunin, Alexey/G-3745-2010; OI Poroikov, Vladimir/0000-0001-7937-2621; Lagunin, Alexey/0000-0003-1757-8004; Nicklaus, Marc/0000-0002-4775-7030 NR 21 TC 96 Z9 103 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JAN-FEB PY 2003 VL 43 IS 1 BP 228 EP 236 DI 10.1021/ci020048r PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 641CA UT WOS:000180725600026 PM 12546557 ER PT J AU Gopich, IV Szabo, A AF Gopich, IV Szabo, A TI Statistics of transitions in single molecule kinetics SO JOURNAL OF CHEMICAL PHYSICS LA English DT Letter ID ENERGY-TRANSFER C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 6 TC 52 Z9 54 U1 0 U2 17 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 1 PY 2003 VL 118 IS 1 BP 454 EP 455 DI 10.1063/1.1523896 PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 626NP UT WOS:000179879500054 ER PT J AU Leff, MK Moolchan, ET Cookus, BA Spurgeon, L Evans, LA London, ED Kimes, A Schroeder, JR Ernst, M AF Leff, MK Moolchan, ET Cookus, BA Spurgeon, L Evans, LA London, ED Kimes, A Schroeder, JR Ernst, M TI Predictors of smoking initiation among at risk youth: A controlled study SO JOURNAL OF CHILD & ADOLESCENT SUBSTANCE ABUSE LA English DT Article DE adolescent smoking; behavioral predictors; psychiatric co-morbidity; at risk youth; smoking initiation ID SUBSTANCE USE DISORDERS; CIGARETTE-SMOKING; TOBACCO SMOKING; DEPRESSIVE-DISORDERS; NICOTINE DEPENDENCE; EARLY ADULTHOOD; DRUG-USE; ADOLESCENTS; CHILDREN; ADHD AB Purpose: To examine smoking initiation in a group of adolescents at risk for developing substance abuse. Methods: Fifty-nine adolescents (25 control and 34 at risk adolescents) participated in a longitudinal study of behavioral and cognitive predictors of development of substance abuse. Aggression, conduct problems, hyperactivity, impulsivity, inattention, anxiety/depression, social difficulties, and somatic complaints were assessed at study entry, and tested as predictors for,smoking. Results: At the last follow-up (mean 15 months), 41 (69.5%) adolescents had not smoked, 10 (17%) had experimented with cigarettes, and 8 (13.5%) had smoked regularly. Aggression, hyperactivity, and somatic complaints significantly predicted smoking initiation (p < 0.05). Smoking status was similar across psychiatric diagnostic groups. Conclusions: These adolescents warrant close monitoring a they are at risk for nicotine dependence and/or psychiatric problems. Preventive measures should be targeted to these at risk adolescents in both primary care and community settings. (C) 2003 by The Haworth Press, Inc. All rights reserved. C1 NIMH, MAP, NIH, Bethesda, MD 20892 USA. NIA, Neuroimaging Branch, Baltimore, MD USA. NIA, Clin Pharmacol & Treatment Res Branch, Baltimore, MD USA. NIA, Intramural Res Program, Baltimore, MD USA. Univ Calif Los Angeles, NPI, Inst Neuropsychiat, Los Angeles, CA USA. RP Ernst, M (reprint author), NIMH, MAP, NIH, 15K N Dr,Room 118,MSC 2670, Bethesda, MD 20892 USA. NR 50 TC 11 Z9 11 U1 3 U2 11 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1067-828X J9 J CHILD ADOLES SUBST JI J. Child Adolesc. Subst. Abus. PY 2003 VL 13 IS 1 BP 59 EP 75 DI 10.1300/J029v13n01_04 PG 17 WC Substance Abuse SC Substance Abuse GA 755XQ UT WOS:000187437100004 ER PT J AU Snider, LA Swedo, SE AF Snider, LA Swedo, SE TI Childhood-onset obsessive-compulsive disorder and tic disorders: Case report and literature review SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; A STREPTOCOCCAL INFECTIONS; SYDENHAMS CHOREA; RHEUMATIC-FEVER; TOURETTES-SYNDROME; INTRAVENOUS IMMUNOGLOBULIN; PLASMA-EXCHANGE; BASAL GANGLIA; ANTIBODIES; CHILDREN AB A subgroup of childhood-onset obsessive-compulsive disorder (OCD) and tic disorders has been found to have a postinfectious autoimmune-mediated etiology. Clinical observations and systematic investigations have shown that a subgroup of children with OCD and/or tic disorders have the onset and subsequent exacerbations of their symptoms following infections with group A beta-hemolytic streptococci (GABHS). This subgroup has been designated by the acronym PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and the temporal association between symptom exacerbations and GABHS infections. The proposed poststreptococcal inflammatory etiology provides a unique opportunity for treatment and prevention, including immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin. A placebo-controlled trial revealed that both intravenous immunoglobulin and plasma exchange were effective in reducing neuropsychiatric symptom severity (40 and 55% reductions, respectively) for a group of severely ill children in the PANDAS subgroup. Further research is required to determine why the treatments are helpful and to ascertain whether or not antibiotic prophylaxis can help prevent poststreptococcal symptom exacerbations. C1 NIMH, Pediat & Dev Neuropsychiat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Snider, LA (reprint author), 10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA. NR 41 TC 19 Z9 19 U1 4 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PY 2003 VL 13 SU 1 BP S81 EP S88 PG 8 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 704HZ UT WOS:000184335400009 PM 12880503 ER PT J AU Kintzel, PE Eastlund, T Calis, KA AF Kintzel, PE Eastlund, T Calis, KA TI Extracorporeal removal of antimicrobials during plasmapheresis SO JOURNAL OF CLINICAL APHERESIS LA English DT Article DE pharmacokinetics; drugs; medications; clearance; antibiotics; dosages; plasma exchange ID PLASMA-EXCHANGE; VANCOMYCIN REMOVAL; COMPARATIVE PHARMACOKINETICS; CEFTAZIDIME; CEFTRIAXONE; ACYCLOVIR; DISPOSITION; ELIMINATION; MOXALACTAM; VOLUNTEERS C1 NIH, Drug Informat Serv, Dept Pharm, Warren G Magnuson Clin Ctr,DHHS, Bethesda, MD 20892 USA. Univ Minnesota, Fairview Univ, Med Ctr, Div Transfus Med, Minneapolis, MN 55455 USA. Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharm Practice, Detroit, MI 48201 USA. RP Kintzel, PE (reprint author), POB 1827, Grand Rapids, MI 49501 USA. NR 37 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0733-2459 J9 J CLIN APHERESIS JI J. Clin. Apheresis PY 2003 VL 18 IS 4 BP 194 EP 205 DI 10.1002/jca.10074 PG 12 WC Hematology SC Hematology GA 758ZK UT WOS:000187712500007 PM 14699597 ER PT J AU Aeschbach, D Sher, L Postolache, TT Matthews, JR Jackson, MA Wehr, TA AF Aeschbach, D Sher, L Postolache, TT Matthews, JR Jackson, MA Wehr, TA TI A longer biological night in long sleepers than in short sleepers SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CIRCADIAN PACEMAKER; INBRED MICE; MELATONIN; TEMPERATURE; RHYTHMS; HUMANS; WAKEFULNESS; PHOTOPERIOD; PROPENSITY; DAYTIME AB Habitual sleep duration varies greatly among individuals. The physiological basis of this variation is unknown. We sought to determine whether individual differences in sleep duration are associated with systematic differences in the duration of the biological night that is programmed by the circadian pacemaker and reflected in the nocturnal interval of circadian rhythms in neuroendocrine function, body temperature, and arousal. Ten young, healthy long sleepers (sleep duration >9 h) and 14 short sleepers (<6 h) were studied under constant environmental conditions and in the absence of sleep. The nocturnal intervals of high plasma melatonin levels, increasing cortisol levels, low body temperature, and increasing sleepiness were longer in long sleepers than in short sleepers. The maxima in cortisol and sleepiness exhibited a close relationship to habitual wake-up time, which occurred approximately 2.5 h later in long sleepers than in short sleepers. It is concluded that the circadian pacemaker programs a longer biological night in long sleepers than in short sleepers. We propose that individual differences in the circadian pacemaker's program may contribute to the variability of sleep duration in the general population. The persistence or inertia of an individual's circadian program, as was evident in constant conditions, may underlie the commonly experienced difficulty of changing habitual sleep duration willfully. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Sleep Med, Boston, MA 02115 USA. NIMH, Mood & Anxiety Disorders Program, Sect Biol Rhythms, Bethesda, MD 20892 USA. Columbia Univ, Dept Psychiat, New York, NY 10032 USA. Univ Texas, Med Branch, Dept Psychiat & Human Behav, Galveston, TX 77555 USA. RP Aeschbach, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Sleep Med, 221 Longwood Ave, Boston, MA 02115 USA. EM daeschbach@hms.harvard.edu NR 39 TC 90 Z9 93 U1 3 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2003 VL 88 IS 1 BP 26 EP 30 DI 10.1210/jc.2002-020827 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636MK UT WOS:000180459700005 PM 12519823 ER PT J AU Ross, JL Roeltgen, D Stefanatos, GA Feuillan, P Kushner, H Bondy, C Cutler, GB AF Ross, JL Roeltgen, D Stefanatos, GA Feuillan, P Kushner, H Bondy, C Cutler, GB TI Androgen-responsive aspects of cognition in girls with Turner syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SPATIAL ABILITY; SEX-DIFFERENCES; WORKING-MEMORY; GROWTH-HORMONE; X-MONOSOMY; CHROMOSOME ABNORMALITIES; BRAIN-DEVELOPMENT; STEROIDS; FEMALES; OXANDROLONE AB Turner syndrome (TS) represents a unique, sex hormone-deficient model in which to study the biological effects of androgen treatment (replacement) on cognition in females because TS girls have gonadal dysgenesis and absent ovarian androgen and estrogen production. We investigated the effects of androgen replacement therapy in TS girls, ages 10-14 yr, on cognitive function. A total of 64 TS girls were randomized to receive oxandrolone or placebo for 2 yr. They had a cognitive evaluation of four domains (verbal abilities, spatial cognition, executive function, and working memory) at baseline, 1, and 2 yr of the study. In addition, all subjects were examined for study safety every 6 months. Three of the four domains studied did not change significantly in response to oxandrolone treatment (verbal abilities, spatial cognition, and executive function). In contrast, the working memory summary score had a significant group by time interaction. The oxandrolone-treated group demonstrated improved performance after 2 yr, compared with the placebo group (P < 0.03). Minimal or no side effects were observed. In conclusion, oxandrolone treatment for 2 yr improves working memory in adolescent girls with TS. What this degree of improvement will mean in real life terms for TS girls remains to tie determined. C1 Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Rehabil, Philadelphia, PA 19107 USA. Alfred I Dupont Hosp Children, Wilmington, DE 19899 USA. Penn State Coll Med, Dept Med, Hershey, PA 17033 USA. Penn State Coll Med, Div Neurol, Hershey, PA 17033 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Biomed Comp Res Inst, Philadelphia, PA 19115 USA. RP Ross, JL (reprint author), Thomas Jefferson Univ, Dept Pediat, Suite 726,1025 Walnut St, Philadelphia, PA 19107 USA. EM Judith.Ross@mail.tju.edu FU NINDS NIH HHS [NS32531] NR 49 TC 43 Z9 44 U1 3 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2003 VL 88 IS 1 BP 292 EP 296 DI 10.1210/jc.2002-021000 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636MK UT WOS:000180459700048 PM 12519868 ER PT J AU Tiosano, D Eisentein, I Militianu, D Chrousos, GP Hochberg, Z AF Tiosano, D Eisentein, I Militianu, D Chrousos, GP Hochberg, Z TI 11 beta-hydroxysteroid dehydrogenase activity in hypothalamic obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTISOL METABOLISM; SEXUAL DIMORPHISM; THYROID-HORMONE; CRANIOPHARYNGIOMA; MODULATION; SECRETION; ADULTS; WEIGHT; MASS; GENE AB After extensive suprasellar operations for hypothalamic tumor removal, some patients develop Cushing-like morbid obesity while they receive replacement doses of glucocorticoids. In this study, we examined the hypothesis that target tissue conversion of inactive 11-ketosteroids to active 11beta-OH glucocorticoids might explain the obesity of some patients with hypothalamic lesions. Toward this aim, we studied 10 patients with hypothalamic obesity and secondary adrenal insufficiency and 6 control Addisonian patients while they were on glucocorticoid replacement therapy. Pituitary hormone deficiencies were replaced when medically indicated. Twentyfour-hour urine was collected after a single oral dose of 12 mg/m(2) hydrocortisone acetate. The ratios of free and conjugated cortisol (F) to cortisone (E) and their metabolites, [tetrahydrocortisol (THF)+5alphaTHF]/tetrahyrdocortisone (THE), dihydrocortisols/dihydrocortisones, cortols/cortolones, and (F+E)/(THF+THE+5alphaTHF), were considered to represent 11beta-hydroxysteroid dehydrogenase (HSD) activity. The 11-OH/11-oxo ratios were significantly higher in the urine of patients with hypothalamic obesity. The 11-OH/11-oxo ratios, however, did not correlate with the degree of obesity, yet a significant correlation was found between conjugated F/E and the ratio of visceral fat to sc fat measured by computerized tomography at the umbilical level. The consequence of increased 11beta-HSD1 activity and the shift of the interconversion toward cortisol may contribute to the effects of the latter in adipose tissue. We propose that deficiency of hypothalamic messengers after surgical injury induces a paracrine/autocrine effect of enhanced glucocorticoid activity due to upregulated 11beta-HSD1 activity. C1 Meyer Childrens Hosp, Dept Pediat, IL-31096 Haifa, Israel. Meyer Childrens Hosp, Dept Radiol, IL-31096 Haifa, Israel. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RP Hochberg, Z (reprint author), Meyer Childrens Hosp, Dept Pediat, POB 9602, IL-31096 Haifa, Israel. EM z_hochberg@rambam.health.gov.il NR 30 TC 51 Z9 52 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2003 VL 88 IS 1 BP 379 EP 384 DI 10.1210/jc.2002-020511 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636MK UT WOS:000180459700060 PM 12519880 ER PT J AU Friedberg, M Zoumakis, E Hiroi, N Bader, T Chrousos, GP Hochberg, Z AF Friedberg, M Zoumakis, E Hiroi, N Bader, T Chrousos, GP Hochberg, Z TI Modulation of 11,8-hydroxysteroid dehydrogenase type 1 in mature human subcutaneous adipocytes by hypothalamic messengers SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-NECROSIS-FACTOR; GROWTH-HORMONE REPLACEMENT; CORTICOTROPIN-RELEASING HORMONE; ADIPOSE STROMAL CELLS; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; FACTOR-ALPHA; TNF-ALPHA; DIFFERENTIAL REGULATION; INSULIN-RESISTANCE; THYROID-HORMONE AB Glucocorticoids are regulated at the prereceptor level by 11beta-hydroxysteroid. dehydrogenase (11beta-HSD), which interconverts inactive cortisone and active cortisol. In a previous study, we noted that patients with hypothalamic obesity had an increased ratio of cortisol/cortisone metabolites, suggesting enhanced 11beta-HSD-1 activity. In this in vitro study, we tested the hypothesis that adipose 11beta-HSD-1 is regulated by the hypothalamus via circulating hormones, sympathetic nervous system innervation, and/or cytokines. Preadipocytes were retrieved from sc fat from healthy nonobese individuals and differentiated in vitro to mature adipocytes. Cells were incubated with several potential effectors, and the activity of 11beta-HSD-1 was assayed by measuring conversion of added 500 nM cortisone to cortisol. Expression of 11beta-HSD-1 mRNA was determined by real-time PCR, whereas lipolytic effects were determined by measuring glycerol concentration in the culture medium. CRH down-regulated 11beta-HSD-1 activity with maximal effect at 10(-9) m (65 +/- 10% of control; P < 0.001) and caused a reduction in lipolysis. Likewise, ACTH down-regulated 11beta-HSD-1 activity with maximal effect at 10(-9) m (65 +/- 20%; P < 0.05) and reduced medium glycerol. Neither CRH nor ACTH affected 11beta-HSD-1 mRNA expression. TNFalpha up-regulated 11beta-HSD-1 activity maximally at 0.6 x 10(-9) M (140 +/- 20%; P < 0.001); the same cytokine increased 11beta-HSD-1 mRNA levels to 3-fold of control (P < 0.05) and increased medium glycerol levels to 165 +/- 14% of control (P < 0.01). IL-1beta also up-regulated 11beta-HSD-1 activity maximally at 0.6 x 10(-9) M (160 +/- 33%; P < 0.001) and caused an increase in glycerol levels (159 +/- 11% of control; P < 0.001). Of the adrenergic agonists, salbutamol. up-regulated 11beta-HSD-1 activity maximally at 10(-7) M (162 +/- 46%; P < 0.02), and clonidine down-regulated it at 10(-7) M (82 +/- 15%; P < 0.005). We conclude that possible distinct hypothalamic mediators regulating adipose tissue 11beta-HSD-1 might include down-regulation of 11beta-HSD-1 activity by CRH, ACTH, and alpha2 sympathetic stimulation, and up-regulation of the enzyme by 132 sympathetic stimulation and by the cytokines TNFalpha and IL-1beta. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RP Hochberg, Z (reprint author), Meyer Childrens Hosp, POB 9602, IL-31096 Haifa, Israel. EM z_hochberg@rambam.health.gov.il NR 66 TC 58 Z9 63 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2003 VL 88 IS 1 BP 385 EP 393 DI 10.1210/jc.2002-020510 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636MK UT WOS:000180459700061 PM 12519881 ER PT J AU Huang, SC Torres-Cruz, J Pack, SD Koch, CA Vortmeyer, AO Mannan, P Lubensky, IA Gagel, RF Zhuang, ZP AF Huang, SC Torres-Cruz, J Pack, SD Koch, CA Vortmeyer, AO Mannan, P Lubensky, IA Gagel, RF Zhuang, ZP TI Amplification and overexpression of mutant RET in multiple endocrine neoplasia type 2-associated medullary thyroid carcinoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROTOONCOGENE; ALLELE; DUPLICATION; DISEASE AB We have previously identified two second hit mechanisms involved in the development of multiple endocrine neoplasia type2 (MEN 2)-associated tumors: trisomy 10 with duplication of the mutant RET allele and loss of the wild-type RET allele. However, some of the MEN 2-associated tumors investigated did not demonstrate either mechanism. Here, we studied the TT cell line derived from MEN 2-associated medullary thyroid carcinoma with a RET germline mutation in codon 634, for alternative mechanisms of tumorigenesis. Although we observed a 2:1 ratio between mutant and wild-type RET at the genomic DNA level in this cell line, fluorescence in situ hybridization analysis revealed neither trisomy 10 nor loss of the normal chromosome 10. Instead, a tandem duplication event was responsible for amplification of mutant RET. In further studies we could for the first time demonstrate that the genomic chromosome 10 abnormalities in this cell line cause an increased production of mutant RET mRNA. These findings provide evidence for a third second hit mechanism resulting in overrepresentation and overexpression of mutant RET in MEN 2-associated tumors. C1 Natl Inst Neurol Disorders & Stroke, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Child Hlth & Human Dis, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Koch, CA (reprint author), Uniklin, Dept Endocrinol Nephrol, Philipp Rosenthalstr 27, D-04103 Leipzig, Germany. EM kochc@exchange.nih.gov RI Koch, Christian/A-4699-2008; Pack, Svetlana/C-2020-2014 OI Koch, Christian/0000-0003-0678-1242; Koch, Christian/0000-0003-3127-5739; NR 13 TC 34 Z9 39 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2003 VL 88 IS 1 BP 459 EP 463 DI 10.1210/jc.2002-021254 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636MK UT WOS:000180459700070 PM 12519890 ER PT J AU West, KA Brognard, J Clark, AS Linnoila, IR Yang, XW Swain, SM Harris, C Belinsky, S Dennis, PA AF West, KA Brognard, J Clark, AS Linnoila, IR Yang, XW Swain, SM Harris, C Belinsky, S Dennis, PA TI Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LUNG-CANCER CELLS; PROTEIN-KINASE-B; ACETYLCHOLINE-RECEPTORS; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; GROWTH-FACTOR; A/J MICE; SURVIVAL; EXPRESSION; APOPTOSIS AB Tobacco-related diseases such as lung cancer cause over 4.2 million deaths annually, with approximately 400,000 deaths per year occurring in the US. Genotoxic effects of tobacco components have been described, but effects on signaling pathways in normal cells have not been described. Here, we show activation of the serine/threonine kinase Akt in nonimmortalized human airway epithelial cells in vitro by two components of cigarette smoke, nicotine and the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Activation of Akt by nicotine or NNK occurred within minutes at concentrations achievable by smokers and depended upon alpha(3)-/alpha(4)-containing or alpha(7)-containing nicotinic acetylcholine receptors, respectively. Activated Akt increased phosphorylation of downstream substrates such as GSK-3, p70(S6K), 4EBP-1, and FKHR. Treatment with nicotine or NNK attenuated apoptosis caused by etoposide, ultraviolet irradiation, or hydrogen peroxide and partially induced a transformed phenotype manifest as loss of contact inhibition and loss of dependence on exogenous growth factors or adherence to ECM. In vivo, active Akt was detected in airway epithelial cells and lung tumors from NNK-treated A/J mice, and in human lung cancers derived from smokers. Redundant Akt activation by nicotine and NNK could contribute to tobacco-related carcinogenesis by regulating two processes critical for tumorigenesis, cell growth and apoptosis. C1 NCI, Canc Therapeut Branch, Bethesda, MD 20889 USA. NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Lovelace Resp Res Inst, Albuquerque, NM USA. RP Dennis, PA (reprint author), NCI, Canc Therapeut Branch, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. OI Swain, Sandra/0000-0002-1320-3830 NR 48 TC 377 Z9 398 U1 1 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2003 VL 111 IS 1 BP 81 EP 90 DI 10.1172/JCI200316147 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 632MT UT WOS:000180227600013 PM 12511591 ER PT J AU Cokic, VP Smith, RD Beleslin-Cokic, BB Njoroge, JM Miller, JL Gladwin, MT Schechter, AN AF Cokic, VP Smith, RD Beleslin-Cokic, BB Njoroge, JM Miller, JL Gladwin, MT Schechter, AN TI Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SICKLE-CELL-ANEMIA; GLOBIN GENE-EXPRESSION; MESSENGER-RNA LEVELS; PROTEIN-KINASE; RIBONUCLEOTIDE REDUCTASE; ERYTHROID PROGENITORS; K562 CELLS; DIFFERENTIAL REGULATION; COLONY GROWTH; DNA-SYNTHESIS AB Hydroxyurea treatment of patients with sickle-cell disease increases fetal hemoglobin (HbF), which reduces hemoglobin S polymerization and clinical complications. Despite its use in the treatment of myeloproliferative diseases for over 30 years, its mechanism of action remains uncertain. Recent studies have demonstrated that hydroxyurea generates the nitric oxide (NO) radical in vivo, and we therefore hypothesized that NO-donor properties might determine the hemoglobin phenotype. We treated both K562 erythroleukemic cells and human erythroid progenitor cells with S-nitrosocysteine (CysNO), an NO donor, and found similar dose- and time-dependent induction of gamma-globin mRNA and HbF protein as we observed with hydroxyurea. Both hydroxyurea and CysNO increased cGMP levels, and the guanylyl cyclase inhibitors ODQ, NS 2028, and LY 83,538 abolished both the hydroxyurea- and CysNO-induced gamma-globin expression. These data provide strong evidence for an NO-derived mechanism for HbF induction by hydroxyurea and suggest possibilities for therapies based on NO-releasing or -potentiating agents. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Med Res Inst, Belgrade, Yugoslavia. NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Schechter, AN (reprint author), NIDDKD, Biol Chem Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 9N307, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 51 TC 168 Z9 173 U1 3 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2003 VL 111 IS 2 BP 231 EP 239 DI 10.1172/JCI200316672 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 640DT UT WOS:000180672900014 PM 12531879 ER PT J AU Gaydos, CA Quinn, TC Willis, D Weissfeld, A Hook, EW Martin, DH Ferrero, DV Schachter, J AF Gaydos, CA Quinn, TC Willis, D Weissfeld, A Hook, EW Martin, DH Ferrero, DV Schachter, J TI Performance of the APTIMA Combo 2 assay for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in female urine and endocervical swab specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; SEXUALLY-TRANSMITTED DISEASES; FAMILY-PLANNING CLINICS; TRANSCRIPTION-MEDIATED AMPLIFICATION; PELVIC INFLAMMATORY DISEASE; AMPLICOR CT/NG TESTS; COBAS AMPLICOR; MULTICENTER EVALUATION; COST-EFFECTIVENESS; DNA AMPLIFICATION AB The greater sensitivity of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae permits the use of urine and other noninvasive specimens, which can increase the reach and decrease the costs of public health screening programs aimed at controlling these infections. This study evaluated the performance of the APTIMA Combo 2 assay, a multiplex assay based on the transcription-mediated amplification reaction, for the simultaneous detection of both pathogens in endocervical swab and urine specimens from females. Combo 2 assay results were compared with patient infected status, which were available by using other commercial NAATs. Sensitivity and specificity for C. trachomatis were 94.2 and 97.6%, respectively, in swabs and 94.7 and 98.9%, respectively, in first-catch urine (FCU). Sensitivity and specificity for N. gonorrhoeae were 99.2 and 98.7%, respectively, in swabs and 91.3 and 99.3%, respectively, in FCU. The assay reliably detected both infections in coinfected patients. The Combo 2 assay can be recommended for use with endocervical swab and urine specimens from females, especially for screening tests for asymptomatic women in sexually transmitted disease surveillance programs. This Food and Drug Administration-cleared assay can be a useful tool in efforts to reduce the prevalence and incidence of C. trachomatis and N. gonorrhoeae infections in sexually active women and to prevent their costly and serious sequelae. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Florida State Dept Hlth, Jacksonville, FL USA. Microbiol Specialists Inc, Houston, TX USA. Univ Alabama, Birmingham, AL USA. Louisiana State Univ, New Orleans, LA 70112 USA. San Joaquin Cty Publ Hlth Serv, Stockton, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Div Infect Dis, Med 1159 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 38 TC 120 Z9 122 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2003 VL 41 IS 1 BP 304 EP 309 DI 10.1128/JCM.41.1.304-309.2003 PG 6 WC Microbiology SC Microbiology GA 635NY UT WOS:000180406700048 PM 12517865 ER PT J AU Kiratisin, P Fukuda, CD Wong, A Stock, F Preuss, JC Ediger, L Fischer, SH Fedorko, DP Witebsky, FG Gill, VJ Brahmbhatt, TN AF Kiratisin, P Fukuda, CD Wong, A Stock, F Preuss, JC Ediger, L Fischer, SH Fedorko, DP Witebsky, FG Gill, VJ Brahmbhatt, TN TI Searching for Bacillus anthracis in suspect powders: a French experience - Authors' reply SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter C1 NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Microbiol Serv, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Clin Pathol Serv, Bethesda, MD 20889 USA. RP Kiratisin, P (reprint author), NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Microbiol Serv, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2003 VL 41 IS 1 BP 524 EP 525 DI 10.1128/JCM.41.1.524-525.2003 PG 2 WC Microbiology SC Microbiology GA 635NY UT WOS:000180406700100 ER PT J AU Blaney, SM Heideman, R Berg, S Adamson, P Gillespie, A Geyer, JR Packer, R Matthay, K Jaeckle, K Cole, D Kuttesch, N Poplack, DG Balis, FM AF Blaney, SM Heideman, R Berg, S Adamson, P Gillespie, A Geyer, JR Packer, R Matthay, K Jaeckle, K Cole, D Kuttesch, N Poplack, DG Balis, FM TI Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CEREBROSPINAL-FLUID; NONHUMAN-PRIMATES; PLASMA; TUMORS AB Purpose : A phase I trial of intrathecal (IT) topotecan was performed to determine the optimal dose, the dose-limiting toxic effects, and the incidence and severity of other toxic effects in patients 3 years and older with neoplastic meningitis. Patients and Methods: Twenty-three assessable patients received IT topotecan administered by means of either lumbar puncture or an indwelling ventricular access device (Ommaya reservoir). Intrapatient dose escalation from 0.025 mg to 0.2 mg was performed in the first cohort of patients. Subsequent cohorts of patients were treated at fixed dose levels of 0.2 mg, 0.4 mg, or 0.7 mg. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. Results: Arachnoiditis, characterized by fever, nausea, vomiting, headache, and back pain, was the dose-limiting toxic effect in two of four patients enrolled at the 0.7 mg dose level. The maximum-tolerated dose (MTD) was 0.4 mg. Six of the 23 assessable patients had evidence of benefit manifested as prolonged disease stabilization or response. Conclusion: The MTD and recommended phase II dose of IT topotecan in patients who are 3 years or older is 0.4 mg. A phase II trial of IT topotecan in children with neoplastic meningitis is in progress 2003 by American Society of Clinical Oncology. C1 Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. MD Anderson Canc Ctr, Houston, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Blaney, SM (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, 6621 Fannin,MC 3-3320, Houston, TX 77030 USA. EM sblaney@txccc.org NR 11 TC 45 Z9 47 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2003 VL 21 IS 1 BP 143 EP 147 DI 10.1200/JCO.2003.04.053 PG 5 WC Oncology SC Oncology GA 685UF UT WOS:000183281100023 PM 12506183 ER PT J AU Maples, HD James, LP Stowe, CD Jones, DP Hak, EB Blumer, JL Vogt, B Wilson, JT Kearns, GL Wells, TG AF Maples, HD James, LP Stowe, CD Jones, DP Hak, EB Blumer, JL Vogt, B Wilson, JT Kearns, GL Wells, TG CA Network Pediat Pharmacology Res Un TI Famotidine disposition in children and adolescents with chronic renal insufficiency SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2002 CL ATLANTA, GEORGIA SP Amer Soc Clin Pharmacol Therapeut ID PEDIATRIC-PATIENTS; ACID-SECRETION; PHARMACOKINETICS; FAILURE; PHARMACODYNAMICS; INFANTS; PLASMA AB The pharmacokinetics of intravenous famotidine (0.5 mg/kg, maximum 20 mg) were evaluated in 18 pediatric patients (ages 1-18 years) with stable, chronic renal insufficiency. Subjects were stratified by calculated creatinine clearance (Cl-cr) into mild (Cl-cr greater than or equal to 50 to < 90 mL/min/1.73 m(2)), moderate (Cl-cr greater than or equal to 25 to < 50 mL/min/1.73 m(2)), and severe (Cl-cr less than or equal to 10 mL/min/ 1.73 m(2)) renal insufficiency groups. Significant differences between the mild, moderate, and severe groups were found for elimination rate (K-el), apparent elimination half-life (t(1/2)), area under the curve (AUC), and total plasma clearance (Cl-p) (p < 0.01). Famotidine renal clearance (Cl-r) was found to be significantly different between the mild and severe groups (p < 0.05). A linear relationship was observed between Cl-cr and Cl-p (p < 0.0001; R-2 = 0.70). No significant differences in nonrenal clearance (Cl-nr) were found between groups; however, Cl-nr as a percentage of Cl-p was significantly different in the severe group (92.9% +/- 7.3% Cl-nr) compared to the combined mild and moderate groups (21.9% +/- 45.6% Cl-nr) (P < 0.05). It was concluded that the pharmacokinetics of famotidine are significantly altered in children with chronic renal insufficiency; accordingly, dosing should be based on glomerular filtration rate (i.e., Cl-cr). C1 Univ Arkansas Med Sci, Sect Pediat Clin Pharmacol & Toxicol, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Tennessee, Memphis, TN USA. Lebonheur Childrens Hosp & Med Ctr, Memphis, TN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Louisiana State Univ, Hlth Serv, Shreveport, LA 71105 USA. Univ Missouri, Kansas City, MO 64110 USA. Childrens Mercy Hosp & Clin, Kansas City, MO USA. NICHHD, NICHD, NIH, Bethesda, MD 20892 USA. RP James, LP (reprint author), Univ Arkansas Med Sci, Sect Pediat Clin Pharmacol & Toxicol, 800 Marshall St,Slot 512, Little Rock, AR 72202 USA. FU NICHD NIH HHS [1 U10 HD 31324-06] NR 22 TC 6 Z9 6 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2003 VL 43 IS 1 BP 7 EP 14 DI 10.1177/0091270002239700 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 629YD UT WOS:000180079400001 PM 12520622 ER PT J AU Lee, CR Pieper, JA Frye, RF Hinderliter, AL Blaisdell, JA Goldstein, JA AF Lee, CR Pieper, JA Frye, RF Hinderliter, AL Blaisdell, JA Goldstein, JA TI Tolbutamide, flurbiprofen, and losartan as probes of CYP2C9 activity in humans SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID HUMAN LIVER-MICROSOMES; PERFORMANCE LIQUID-CHROMATOGRAPHY; HEPATIC CYTOCHROME-P450 2C9; STEREOSELECTIVE METABOLISM; ALLELIC VARIANT; HUMAN PLASMA; PHARMACOKINETICS; ENZYMES; URINE; HYDROXYLATION AB The metabolic activity of CYP2C9 in 16 subjects expressing four different genotypes (CYP2C9*1/*1, *1/*2, *1/*3, and *2/*2) was evaluated. Single oral doses of tolbutamide, flurbiprofen, and losartan were administered in a randomized, crossover design. Plasma and urine were collected over 24 hours. The urinary metabolic ratio and amount of metabolite(s) excreted were correlated with formation clearance. The formation clearance of tolbutamide to its CYP2C9-mediated metabolites demonstrated a stronger association with genotype compared to flurbiprofen and losarton, respectively (r(2) = 0.64 vs. 0.53 vs. 0.42). A statistically significant correlation was observed between formation clearance of tolbutamide and the 0- to 12-hour urinary amount of 4'-hydroxy-tolbutamide and carboxytolbutamide (r = 0.84). Compared to tolbutamide, the correlations observed between the respective measures of flurbiprofen and losartan metabolism were not as strong. Tolbutamide is a better CYP2C9 probe than flurbiprofen and losartan, and the 0- to 12-hour amount of 4'-hydroxytolbutomide and carboxytolbutamide is the best urinary measure of its metabolism. C1 Univ N Carolina, Div Pharmacotherapy, Chapel Hill, NC 27599 USA. Univ N Carolina, Div Cardiol, Chapel Hill, NC 27599 USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Pieper, JA (reprint author), Univ N Carolina, Div Pharmacotherapy, CB 7360,Beard Hall, Chapel Hill, NC 27599 USA. RI Goldstein, Joyce/A-6681-2012; OI Lee, Craig/0000-0003-3595-5301; Frye, Reginald/0000-0002-1841-1401 FU NCRR NIH HHS [RR00046] NR 34 TC 68 Z9 69 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2003 VL 43 IS 1 BP 84 EP 91 DI 10.1177/0091270002239710 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 629YD UT WOS:000180079400011 PM 12520632 ER PT J AU Gray, NA Zhou, R Du, J Moore, GJ Manji, HK AF Gray, NA Zhou, R Du, J Moore, GJ Manji, HK TI The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID GLYCOGEN-SYNTHASE KINASE-3-BETA; NEUROBLASTOMA SH-SY5Y CELLS; MANIC-DEPRESSIVE ILLNESS; SIGNAL-TRANSDUCTION PATHWAYS; CHRONIC LITHIUM TREATMENT; LOW SERUM LEVELS; BIPOLAR DISORDER; GENE-EXPRESSION; MAJOR DEPRESSION; TRANSCRIPTION FACTOR AB Mood disorders have traditionally been conceptualized as neurochemical disorders, but there is now evidence from a variety of sources demonstrating regional reductions in central nervous system (CNS) volume, as well as reductions in the numbers and/or sizes of glia and neurons in discrete brain areas. Although the precise cellular mechanisms underlying these morphometric changes remain to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that lithium and valproate have recently been demonstrated to robustly increase the expression of the cytoprotective protein bcl-2 (an abbreviation for the B-cell lymphoma/leukemia-2 gene) in the CNS in vivo and in cells of human neuronal origin. Lithium and valproate also robustly activate a signaling cascade utilized by endogenous growth factors-the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. Complementary human studies have shown that chronic lithium administration significantly increases gray matter content in a regionally selective manner, suggesting a reversal of illness-related atrophy and an increase in the volume of the neuropil. These unique and unexpected properties of lithium and valproate suggest that they may have broader utility as adjunctive agents in the treatment of a variety of neuropsychiatric disorders associated with cell atrophy or loss. The adjunctive use of these agents-at low doses-may provide the trophic support necessary to restore, enhance, and maintain normal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal functioning. C1 NIMH, Lab Mol Pathophysiol, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Mol Pathophysiol Lab, Detroit, MI USA. RP Manji, HK (reprint author), NIMH, Lab Mol Pathophysiol, Bldg 49,Room B1EE16,49 Convent Dr,MSC 4405, Bethesda, MD 20892 USA. RI Moore, Gregory/E-7184-2010 OI Moore, Gregory/0000-0001-8541-3194 NR 139 TC 44 Z9 47 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2003 VL 64 SU 5 BP 3 EP 17 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 677UR UT WOS:000182826800001 PM 12720479 ER PT J AU Wan, HH Li, LG Federhen, S Wootton, JC AF Wan, HH Li, LG Federhen, S Wootton, JC TI Discovering simple regions in biological sequences associated with scoring schemes SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE complexity; biological sequence; simple region; scoring scheme; search masking; nonglobular domain ID ACID SUBSTITUTION MATRICES; AMINO-ACID; NUCLEOTIDE-SEQUENCES; LOCAL COMPLEXITY; DATABASES; PROTEINS AB Let A denote an alphabet consisting of n types of letters. Given a sequence S of length L with v(i) letters of type i on A, to describe the compositional properties and combinatorial structure of S, we propose a new complexity function of S, called the reciprocal complexity of S, as [GRAPHICS] Based on this complexity measure, an efficient algorithm is developed for classifying and analyzing simple segments of protein and nucleotide sequence databases associated with scoring schemes. The running time of the algorithm is nearly proportional to the sequence length. The program DSR corresponding to the algorithm was written in C++, associated with two parameters (window length and cutoff value) and a scoring matrix. Some examples regarding protein sequences illustrate how the method can be used to find regions. The first application of DSR is the masking of simple sequences for searching databases. Queries masked by DSR returned a manageable set of hits below the E-value cutoff score, which contained all true positive homologues. The second application is to study simple regions detected by the DSR program corresponding to known structural features of proteins. An extensive computational analysis has been made of protein sequences with known, physicochemically defined nonglobular segments. For the SWISS-PROT amino acid sequence database (Release 40.2 of 02-Nov-2001), we determine that the best parameters and the best BLOSUM matrix are, respectively, for automatic segmentation of amino acid sequences into nonglobular and globular regions by the DSR program: Window length k = 35, cutoff value b = 0.46, and the BLOSUM 62.5 matrix. The average "agreement accuracy (sensitivity)" of DSR segmentation for the SWISS-PROT database is 97.3%. C1 Natl Ctr Genome Resources, Santa Fe, NM 87505 USA. Second Army Med Univ, Dept Protect Med, Nanjing Army Med Coll, Nanjing 210099, Peoples R China. Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wan, HH (reprint author), Natl Ctr Genome Resources, 2935 Rodeo Pk Dr E, Santa Fe, NM 87505 USA. FU NIGMS NIH HHS [R01-GM0002511] NR 23 TC 15 Z9 16 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2003 VL 10 IS 2 BP 171 EP 185 DI 10.1089/106652703321825955 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 680NX UT WOS:000182985200005 PM 12804090 ER PT J AU Mumey, BM Bailey, BW Kirkpatrick, B Jesaitis, AJ Angel, T Dratz, EA AF Mumey, BM Bailey, BW Kirkpatrick, B Jesaitis, AJ Angel, T Dratz, EA TI A new method for mapping discontinuous antibody epitopes to reveal structural features of proteins SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article; Proceedings Paper CT 6th Annual International Conference on Computational Biology (RECOMB 2002) CY APR 18-21, 2002 CL WASHINGTON, D.C. DE protein structure; antibody imprinting; epitope mapping; protein surface graphs ID PHAGE-DISPLAY; COUPLED RECEPTORS; ATOMIC-STRUCTURE; IDENTIFICATION; GENOMICS; RECOGNITION; PREDICTION; ALGORITHM; RHODOPSIN; PEPTIDES AB Antibodies that bind to protein surfaces of interest can be used to report the three-dimensional structure of the protein as follows: Proteins are composed of linear polypeptide chains that fold together in complex spatial patterns to create the native protein structure. These folded structures form binding sites for antibodies. Antibody binding sites are typically "assembled" on the protein surface from segments that are far apart in the primary amino acid sequence of the target proteins. Short amino acid probe sequences that bind to the active region of each antibody can be used as witnesses to the antibody epitope surface and these probes can be efficiently selected from random sequence peptide libraries. This paper presents a new method to align these antibody epitopes to discontinuous regions of the one-dimensional amino acid sequence of a target protein. Such alignments of the epitopes indicate how segments of the protein sequence must be folded together in space and thus provide long-range constraints for solving the 3-D protein structure. This new antibody-based approach is applicable to the large fraction of proteins that are refractory to current approaches for structure determination and has the additional advantage of requiring very small amounts of the target protein. The binding site of an antibody is a surface, not just a continuous linear sequence, so the epitope mapping alignment problem is outside the scope of classical string alignment algorithms, such as Smith-Waterman. We formalize the alignment problem that is at the heart of this new approach, prove that the epitope mapping alignment problem is NP-complete, and give some initial results using a branch-and-bound algorithm to map two real-life cases. Initial results for two validation cases are presented for a graph-based protein surface neighbor mapping procedure that promises to provide additional spatial proximity information for the amino acid residues on the protein surface. C1 Montana State Univ, Dept Comp Sci, Bozeman, MT 59717 USA. NIAAA, NIH, DICBR, LMBB, Bethesda, MD 20892 USA. Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. RP Mumey, BM (reprint author), Montana State Univ, Dept Comp Sci, Bozeman, MT 59717 USA. EM mumey@coe.montana.edu RI Bailey, Brian/B-1732-2009 FU NIAID NIH HHS [R01 AI 26711, R01 AI 22735]; NIGMS NIH HHS [R01 GM 62547] NR 38 TC 32 Z9 37 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2003 VL 10 IS 3-4 BP 555 EP 567 DI 10.1089/10665270360688183 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 707XT UT WOS:000184535800020 PM 12935344 ER PT J AU Bailey, JJ Hodges, M Church, TR AF Bailey, JJ Hodges, M Church, TR TI Risk stratification in diabetic patients with a previous myocardial infarction SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 28th Annual ISCE Conference CY APR 26-MAY 01, 2003 CL SNOWBIRD, UTAH SP ISCE ID HEART-RATE-VARIABILITY; DEFIBRILLATOR; TRIALS; DEATH AB We used Kaplan-Meier 2-year survival analysis on CAST registry patients to estimate prognostic power of VPC frequency (greater than or equal to10/hr), presence of nonsustained ventricular tachycardia (NSVT), left ventricular ejection fraction, and presence of diabetes. We also used meta-analysis of reports in the literature to estimate prognostic power of signal-averaged electrocardiogram (SAECG) and electrophysiological tests (EPS) as well as VPCs, NSVT, and LVEF. Combined results from CAST analysis and literature meta-analysis yielded sensitivity and specificity for VPCs, NSVT, SAECG, LVEF, Diabetes, and EPS. The overall 2 year event rate for life-threatening arrhythmias or death was 7.88% for 51,144 cases in the combined CAST and literature data. After segmenting the population 21.3% were diabetic with a predicted 2 yr event rate of 13.5 % and 78.7 % were nondiabetic event rate of 6.4%. We defined low risk as <10% and high risk as greater than or equal to30%. Otherwise predicted event rate was classified as "unstratified." When all possible combination of noninvasive tests were applied, a prominent difference in the proportions of cases at risk between the diabetics and nondiabetics was revealed. When the unstratified cases were subsequently tested with EPS, the difference between the two groups was even more marked. C1 NIH, Ctr Informat Technol, Bethesda, MD USA. Minneapolis Heart Inst Fdn, Minneapolis, MN USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Bailey, JJ (reprint author), NIH, Ctr Informat Technol, Bldg 12A,Room 2007,MSC 5620,9000 Rockville Pike, Bethesda, MD USA. EM jjbailey@helix.nih.gov OI Church, Timothy R./0000-0003-3292-5035 NR 14 TC 0 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2003 VL 36 SU S BP 121 EP 125 DI 10.1016/S0022-0736(03)00123-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 765YX UT WOS:000188319600020 PM 14716612 ER PT J AU Martinez, A Saldise, L Ramirez, MJ Belzunegui, S Zudaire, E Luquin, MR Cuttitta, F AF Martinez, A Saldise, L Ramirez, MJ Belzunegui, S Zudaire, E Luquin, MR Cuttitta, F TI Adrenomedullin expression and function in the rat carotid body SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID TUMOR-CELL LINES; ENDOTHELIAL-CELLS; GROWTH-FACTOR; HYPOXIA; DEGRADATION; METABOLITES; RECOVERY; CHANNELS; PEPTIDE; ENZYMES AB Adrenomedullin (AM) immunoreactivity has been found in granules of the glomus (type 1) cells of the carotid bodies in rats. The identity of these cells was ascertained by colocalization of immunoreactivities for AM and tyrosine hydroxylase in their cytoplasm. Exposure of freshly isolated carotid bodies to synthetic AM resulted in a concentration- and time-dependent degranulation of glomus cells as measured by dopamine (DA) release. DA release reached a zenith 30 min after exposure to AM (94.2% over untreated controls). At this time-point, the response to AM was similar to the one elicited by 5 min of exposure to 100 mM K+. Nevertheless, injection of 1 mul 60 nM AM/g body weight into the tail vein of the rats did not induce statistical differences in DA release from the carotid bodies. Exposure of the oxygen-sensitive cell line PC-12 to hypoxia elicited an increase in AM mRNA expression and peptide secretion into serum-free conditioned medium. Previous data have shown that elevation of AM expression under hypoxia is mediated through hypoxia-inducible factor-1, and that exposure of chromaffin cells to AM results in degranulation. All these data suggest that AM is an important autocrine regulator of carotid body function. C1 NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Navarra, Dept Expt Neurol, E-31080 Pamplona, Spain. Univ Navarra, Dept Pharmacol, E-31080 Pamplona, Spain. RP Martinez, A (reprint author), NCI, Cell & Canc Biol Branch, NIH, Bldg 10,Room 13N262, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013; OI Martinez, Alfredo/0000-0003-4882-4044; Ramirez, Maria Javier/0000-0002-3488-9579 NR 34 TC 14 Z9 14 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JAN PY 2003 VL 176 IS 1 BP 95 EP 102 DI 10.1677/joe.0.1760095 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 641LR UT WOS:000180746700011 PM 12525253 ER PT J AU Miller, AC Brooks, K Stewart, M Anderson, B Shi, L McClain, D Page, N AF Miller, AC Brooks, K Stewart, M Anderson, B Shi, L McClain, D Page, N TI Genomic instability in human osteoblast cells after exposure to depleted uranium: delayed lethality and micronuclei formation SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY LA English DT Article DE heavy-metals; depleted uranium; delayed lethality; micronuclei; osteoblast ID INDUCED CHROMOSOMAL INSTABILITY; IRRADIATED MAMMALIAN-CELLS; HUMAN FIBROBLASTS; PARTICLE IRRADIATION; IONIZING-RADIATION; ALPHA-PARTICLES; X-RAYS; MUTATIONS; TRANSFORMATION; EXPRESSION AB It is known that radiation can induce a transmissible persistent destabilization of the genome. We have established an in vitro cellular model using HOS cells to investigate whether genomic instability plays a role in depleted uranium (DU)-induced effects. Transmissible genomic instability, manifested in the progeny of cells exposed to ionizing radiation, has been characterized by de novo chromosomal aberrations, gene mutations, and an enhanced death rate. Cell lethality and micronuclei formation were measured at various times after exposure to DU, Ni, or gamma radiation. Following a prompt, concentration-dependent acute response for both end-points, there was de novo genomic instability in progeny cells. Delayed reproductive death was observed for many generations (36 days, 30 population doublings) following exposure to DU, Ni, or gamma radiation. While DU stimulated delayed production of micronuclei up to 36 days after exposure, levels in cells exposed to gamma-radiation or Ni returned to normal after 12 days. There was also a persistent increase in micronuclei in all clones isolated from cells that had been exposed to nontoxic concentrations of DU. While clones isolated from gamma-irradiated cells (at doses equitoxic to metal exposure) generally demonstrated an increase in micronuelei, most clonal progeny of Ni-exposed cells did not. These studies demonstrate that DU exposure in vitro results in genomic instability manifested as delayed reproductive death and micronuclei formation. Published by Elsevier Science Ltd. C1 Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, Bethesda, MD 20889 USA. NCI, Div Canc Treatment, Mol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Miller, AC (reprint author), Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 31 TC 65 Z9 67 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0265-931X J9 J ENVIRON RADIOACTIV JI J. Environ. Radioact. PY 2003 VL 64 IS 2-3 SI SI BP 247 EP 259 AR PII S0265-931X(02)00053-X DI 10.1016/S0265-931X(02)00053-X PG 13 WC Environmental Sciences SC Environmental Sciences & Ecology GA 626CR UT WOS:000179855200015 PM 12500809 ER PT J AU Brenner, AV Wang, ZY Kleinerman, RA Lei, SJ Metayer, C Wang, WL Lubin, JH AF Brenner, AV Wang, ZY Kleinerman, RA Lei, SJ Metayer, C Wang, WL Lubin, JH TI Menstrual and reproductive factors and risk of lung cancer among Chinese women, Eastern Gansu Province, 1994-1998 SO JOURNAL OF EPIDEMIOLOGY LA English DT Article DE female; lung neoplasms; risk factors; reproductive history; menstruation ID STEROID-RECEPTORS; FAMILY HISTORY; SEX-HORMONES; ADENOCARCINOMA; ASSOCIATION; CARCINOMA; ESTROGEN AB There are suggestions that women have higher relative risks of lung cancer than men given similar levels of tobacco exposure, implying that sex-related hormones may influence lung cancer risk. We evaluated the association between lung cancer risk and menstrual and reproductive factors on a subset of self-responding females in a population based case-control study in Eastern Gansu Province, China, 1994-1998. The analysis included 109 incident lung cancer cases and 435 controls selected from the census list and frequency matched to cases on age and prefecture. Odds ratios were lower for later ages at menarche (trend, P = 0.015) and later ages at menopause (trend, P = 0.074). Despite limitations, these findings suggest a possible role of hormones in the etiology of lung cancer in females. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, EPS, Bethesda, MD 20892 USA. Minist Publ Hlth, Lab Ind Hyg, Beijing 100088, Peoples R China. RP Brenner, AV (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, EPS, 6120 Execut Blvd,MSC 7362, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01-CP-50509] NR 26 TC 23 Z9 23 U1 0 U2 1 PU JAPAN EPIDEMIOLOGICAL ASSOC PI TOCHIGI PA JICHI MEDICAL SCHOOL, DEPT PUBLIC HEALTH, 3311-1 YAKUSHIJI, MINAMIKAWACH, TOCHIGI, 329-0498, JAPAN SN 0917-5040 J9 J EPIDEMIOL JI J. Epidemiol. PD JAN PY 2003 VL 13 IS 1 BP 22 EP 28 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 735BT UT WOS:000186093100003 PM 12587610 ER PT J AU Parascandola, M AF Parascandola, M TI Objectivity and the neutral expert SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Editorial Material ID EPIDEMIOLOGY; CANCER; HEALTH C1 NCI, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NCI, 6130 Execut Blvd,Suite 3109, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD JAN PY 2003 VL 57 IS 1 BP 3 EP 4 DI 10.1136/jech.57.1.3 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 629XV UT WOS:000180078500003 PM 12490638 ER PT J AU Weed, DL McKeown, RE AF Weed, DL McKeown, RE TI Science, ethics, and professional public health practice SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Editorial Material C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ S Carolina, Norman J Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. RP Weed, DL (reprint author), NCI, Div Canc Prevent, EPS T-41,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 9 TC 12 Z9 12 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD JAN PY 2003 VL 57 IS 1 BP 4 EP 5 DI 10.1136/jech.57.1.4 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 629XV UT WOS:000180078500004 PM 12490639 ER PT J AU Holmgren, M AF Holmgren, M TI Influence of permeant ions on gating in cyclic nucleotide-gated channels SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE ligand-gated channel; cGMP; cAMP; tetracaine; photoreceptor ID GMP-ACTIVATED CHANNEL; OLFACTORY RECEPTOR NEURONS; RECTIFIER POTASSIUM CHANNELS; CARDIAC NA+ CHANNELS; MONO-VALENT CATIONS; ROD OUTER SEGMENT; SHAKER K-CHANNELS; RETINAL RODS; DIVALENT-CATIONS; EXCISED PATCHES AB Cyclic nucleotide-gated channels are key components in the transduction of visual and olfactory signals where their role is to respond to changes in the intracellular concentration of cyclic nucleotides. Although these channels poorly select between physiologically relevant monovalent cations, the gating by cyclic nucleotide is different in the presence of Na+ or K+ ions. This property was investigated using rod cyclic nucleotide-gated channels formed by expressing the subunit 1 (or alpha) in HEK293 cells. In the presence of K+ as the permeant ion, the affinity for cGMP is higher than the affinity measured in the presence of Na+. At the single channel level, sub-saturating concentrations of cGMP show that the main effect of the permeant K+ ions is to prolong the time channels remain open without major changes in the shut time distribution. In addition, the maximal open probability was higher when K+ was the permeant ion (0.99 for K+ vs. 0.95 for Na+) due to an increase in the apparent mean open time. Similarly, in the presence of saturating concentrations of cAMP, known to,bind but unable to efficiently open the channel, permeant K+ ions also prolong the time channels visit the open state. Together, these results suggest that permeant ions alter the stability of the open conformation by influencing of the O-->C transition. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Holmgren, M (reprint author), NINDS, NIH, Bldg 36,Room 2C06,36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA. NR 78 TC 11 Z9 11 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JAN PY 2003 VL 121 IS 1 BP 61 EP 72 DI 10.1085/jgp.20028722 PG 12 WC Physiology SC Physiology GA 634JD UT WOS:000180335500005 PM 12508054 ER PT J AU Dougherty, DM Bjork, JM Moeller, FG Harper, RA Marsh, DM Mathias, CW Swann, AC AF Dougherty, DM Bjork, JM Moeller, FG Harper, RA Marsh, DM Mathias, CW Swann, AC TI Familial transmission of Continuous Performance Test behavior: Attentional and impulsive response characteristics SO JOURNAL OF GENERAL PSYCHOLOGY LA English DT Article DE adolescents; Continuous Performance Test; familial; impulsivity; parents ID SUSTAINED ATTENTION; HYPERACTIVE-CHILDREN; CONDUCT DISORDER; PERSONALITY-DISORDER; LABORATORY MEASURES; TASK-PERFORMANCE; AGGRESSION; ALCOHOL; DISINHIBITION; WOMEN AB Continuous Performance Tests (CPTs) provide information on attentional processing and impulsive behavior. The results of previous research that used self-report measures have provided evidence for familial transmission (through genetic and/or environmental influences) of impulsive characteristics. The authors of the present study examined whether the impulsive behavioral parameters that are measured by the CPT also share familial relationships. The researchers asked 26 healthy parent-adolescent pairs to complete the Immediate and Delayed Memory-Tasks (IMT/DMT; D. M. Dougherty, 1999; D. M. Dougherty, D. M. Marsh, & C. W. Mathias, 2002), a modified CPT (B. A. Cornblatt, N. J. Risch, G. Faris, D. Friedman, & L. Erlenmeyer-Kimling, 1988; H. E. Rosvold, A. Mirsky, I. Sarason, E. D. Breansome, Jr., & L. H. Beck, 1956), and the Barratt Impulsiveness Scale (BIS; J. H. Patton, M. S. Stanford, & E. S. Barratt, 1995), a self-report measure. The main findings can be summarized as follows: (a) commission errors (but not correct detections) on the IMT and DMT were correlated between parents and their adolescent children, (b) adolescents emitted a higher proportion of commission errors than did their parents, and (c) self-reported impulsivity (i.e., BIS) was correlated with commission errors for parents, but not for adolescents. The findings of this study support the use of an objective behavioral measure of impulsivity to assess familial relationships of impulsivity. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Neurobehav Res Lab & Clin, Houston, TX 77030 USA. NIAAA, Clin Studies Lab, NIH, Rockville, MD 20852 USA. RP Dougherty, DM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Neurobehav Res Lab & Clin, 1300 Moursund St, Houston, TX 77030 USA. OI Mathias, Charles/0000-0003-1902-673X FU NIMH NIH HHS [R01-MH63908-01] NR 67 TC 25 Z9 25 U1 2 U2 7 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0022-1309 J9 J GEN PSYCHOL JI J. Gen. Psychol. PD JAN PY 2003 VL 130 IS 1 BP 5 EP 21 PG 17 WC Psychology, Multidisciplinary SC Psychology GA 654JC UT WOS:000181491600001 PM 12635853 ER PT J AU Farrell, S Manning, WG Finch, MD AF Farrell, S Manning, WG Finch, MD TI Alcohol dependence and the price of alcoholic beverages SO JOURNAL OF HEALTH ECONOMICS LA English DT Review DE alcohol; dependence; price; price elasticity ID DSM-III-R; HEALTH INTERVIEW SURVEY; MOTOR-VEHICLE FATALITIES; UNITED-STATES; DRINKING PATTERNS; NATIONAL SURVEY; HEAVY DRINKING; SOCIAL COSTS; BEER TAXES; DEMAND AB This study estimates the impact of the price of alcoholic beverages on latent dimensions of current alcohol dependence and abuse. A three-part econometric model is used to estimate the impact of price on three latent dimensions (factors). For heavier drinking, the estimated price elasticity is -1.325 (P = 0.027); for physical and other consequences of drinking, - 1.895 (P = 0.003); for increased salience of drinking, -0.411 (P = 0.339). For a single latent factor characterized simply as dependence/abuse, estimated price elasticity is -1.487 (P = 0.012). These results suggest that higher prices for alcohol reduce important dimensions of current alcohol dependence and abuse. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. UnitedHlth Grp, Minnetonka, MN USA. RP Farrell, S (reprint author), NIAAA, NIH, 6000 Execut Blvd,Suite 514, Bethesda, MD 20892 USA. RI Stockwell, Tim/B-6662-2012 NR 109 TC 37 Z9 37 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 J9 J HEALTH ECON JI J. Health Econ. PD JAN PY 2003 VL 22 IS 1 BP 117 EP 147 AR PII S0167-6296(02)00099-1 DI 10.1016/S0167-6296(02)00099-1 PG 31 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 635TC UT WOS:000180414400006 PM 12564720 ER PT J AU Neuhauser, L Kreps, GL AF Neuhauser, L Kreps, GL TI Rethinking communication in the E-health era SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Review DE E-health; health behavior; health communication; health informatics; health interventions; participation ID BREAST SELF-EXAMINATION; OF-THE-ART; RANDOMIZED-TRIAL; UNITED-STATES; INFORMATION; INTERNET; BEHAVIOR; IMPACT; INTERVENTIONS; EDUCATION AB There is substantial epidemiological evidence that widespread adoption of specific behavior changes can significantly improve population health. Yet, health communication efforts, while well intentioned, have often failed to engage people to change behavior within the complex contexts of their lives. 'E-health communication', health promotion efforts that are mediated by computers and other digital technologies, may have great potential to promote desired behavior changes through unique features such as mass customization, interactivity and convenience. There is growing initial evidence that e-health communication can improve behavioral outcomes. However, we have much to learn about whether the technical promise of e-health communication will be effective within the social reality of how diverse people communicate and change in the modern world. This article examines current evidence concerning e-health communication and evaluates opportunities for e-health applications. C1 Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Neuhauser, L (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, 140 Warren Hall MC 7360, Berkeley, CA 94720 USA. EM lindan@uclink4.berkeley.edu NR 125 TC 117 Z9 118 U1 3 U2 25 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD JAN PY 2003 VL 8 IS 1 BP 7 EP 23 DI 10.1177/1359105303008001426 PG 17 WC Psychology, Clinical SC Psychology GA 640GZ UT WOS:000180681500002 PM 22113897 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI Challenges in therapy of chronic hepatitis B SO JOURNAL OF HEPATOLOGY LA English DT Article; Proceedings Paper CT EASL International Consensus Conference on Hepatitis B CY SEP 13-14, 2002 CL GENEVA, SWITZERLAND SP EASL ID TERM FOLLOW-UP; E-ANTIGEN; INTERFERON-ALFA; ADEFOVIR DIPIVOXIL; DNA LEVELS; VIRUS-DNA; LAMIVUDINE; CARRIERS; LIVER; TRIAL C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Rm 9A27,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA. NR 22 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2003 VL 39 SU 1 BP S230 EP S235 DI 10.1016/S0168-8278(03)00332-5 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 739VA UT WOS:000186366100038 PM 14708709 ER PT J AU Narfstrom, K Katz, ML Ford, M Redmond, TM Rakoczy, E Bragadottir, R AF Narfstrom, K Katz, ML Ford, M Redmond, TM Rakoczy, E Bragadottir, R TI In vivo gene therapy in young and adult RPE65-/- dogs produces long-term visual improvement SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT Symposium on Advances in Canine and Feline Genomics CY MAY 16-19, 2002 CL ST LOUIS, MISSOURI ID PIGMENT-EPITHELIUM; ADENOASSOCIATED VIRUS; CHILDHOOD BLINDNESS; MICROSOMAL PROTEIN; RETINAL DYSTROPHY; EXPRESSION; MODEL AB Defects in the RPE65 gene, which is selectively expressed in the retinal pigment epithelium (RPE), result in blindness and gradual photoreceptor cell degeneration. Experiments were conducted to assess the efficacy of gene replacement therapy in restoring retinal function in PPE65(-)/(-) dogs. Long-term effects of PPE65 gene therapy were assessed using visual behavioral testing and electroretinographic (ERG) recordings at 10-12 weeks and 6-9 months after surgery in five affected dogs. Subretinal injections of similar dosages of two constructs were performed in affected dogs at the ages of 4-30 months: rAAV.RPE65 into one eye and, in four of five dogs, rAAV.GFP contralaterally. Before surgery all RPE65(-)/(-) dogs were behaviorally blind with either no or very low-amplitude ERG responses to fight stimuli. Marked improvements in visual behavior and ERG responses were observed as early as 4 weeks after surgery in affected animals. Except for fight-adapted 50 Hz ERG flicker responses, all ERG parameters tested increased significantly in the eyes treated with the rAAV.RPE65 construct at the early follow-up. Gradual progressive improvements in ERG responses were observed in the RPE65-treated eyes over time. An unexpected finding was that on long-term follow-up, marked improvement of photopic ERG responses were also observed in the contralateral control eye in both young and older dogs. These results are promising for future clinical trials of human patients with retinal degenerative diseases, such as Leber congenital amaurosis, that result from RPE65 gene defects. C1 Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Visd Sci Grp, Columbia, MO 65211 USA. Univ Missouri, Sch Med, Mason Eye Inst, Dept Ophthalmol, Columbia, MO 65212 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Western Australia, Ctr Ophthalmol & Visual Sci, Nedlands, WA 6009, Australia. Univ Oslo, Ulleval Hosp, Dept Ophthalmol, N-0407 Oslo, Norway. RP Narfstrom, K (reprint author), Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Visd Sci Grp, A379 Clydesdale Hall, Columbia, MO 65211 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 17 TC 75 Z9 80 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD JAN-FEB PY 2003 VL 94 IS 1 BP 31 EP 37 DI 10.1093/jhered/esg015 PG 7 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 670MX UT WOS:000182413500006 PM 12692160 ER PT J AU Menotti-Raymond, M David, VA Chen, ZQ Menotti, KA Sun, S Schaffer, AA Agarwala, R Tomlin, JF O'Brien, SJ Murphy, WJ AF Menotti-Raymond, M David, VA Chen, ZQ Menotti, KA Sun, S Schaffer, AA Agarwala, R Tomlin, JF O'Brien, SJ Murphy, WJ TI Second-generation integrated genetic linkage/radiation hybrid maps of the domestic cat (Felis catus) SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT Symposium on Advances in Canine and Feline Genomics CY MAY 16-19, 2002 CL ST LOUIS, MISSOURI ID NONTEMPLATED NUCLEOTIDE ADDITION; RADIATION HYBRID; LINKAGE MAP; COMPARATIVE GENOMICS; DNA-POLYMERASE; MAMMALS; CONSTRUCTION; POLYMORPHISM; SEQUENCES; EVOLUTION AB We report construction of second-generation integrated genetic linkage and radiation hybrid (RH) maps in the domestic cat (Felis catus) that exhibit a high level of marker concordance and provide near-full genome coverage. A total of 864 markers, including 585 coding loci (type I markers) and 279 polymorphic microsatellite loci (type II markers), are now mapped in the cat genome. We generated the genetic linkage map utilizing a multigeneration interspecies backcross pedigree between the domestic cat and the Asian leopard cat (Prionailurus bengalensis). Eighty-one type I markers were integrated with 247 type II markers from a first-generation map to generate a map of 328 loci (320 autosomal and 8 X-linked) distributed in 47 linkage groups, with an average intermarket spacing of 8 cM. Genome coverage spans approximately 2,650 cM, allowing an estimate for the genetic length of the sex-averaged map as 3,300 cM. The 834-locus second-generation domestic cat RH map was generated from the incorporation of 579 type I and 255 type II loci. Type I markers were added using targeted selection to cover either genomic regions underrepresented in the first-generation map or to refine breakpoints in human/feline synteny. The integrated linkage and RH maps reveal approximately 110 conserved segments ordered between the human and feline genomes, and provide extensive anchored reference marker homologues that connect to the more gene dense human and mouse sequence maps, suitable for positional cloning applications. C1 NCI, Lab Genom Divers, Ft Detrick, Frederick, MD 21702 USA. NCI, Basic Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, IEB, NIH, Bethesda, MD 20894 USA. NIH, IEB, NCBI, CBB, Bethesda, MD 20894 USA. NIH, CIT, CBEL, BIMAS, Bethesda, MD 20892 USA. RP Menotti-Raymond, M (reprint author), NCI, Lab Genom Divers, Ft Detrick, Bldg 560,Rm 11-38, Frederick, MD 21702 USA. RI Schaffer, Alejandro/F-2902-2012 NR 52 TC 73 Z9 73 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD JAN-FEB PY 2003 VL 94 IS 1 BP 95 EP 106 DI 10.1093/jhered/esg008 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 670MX UT WOS:000182413500015 PM 12692169 ER PT J AU Parle-McDermott, A Mills, JL Kirke, PN O'Leary, VB Swanson, DA Pangilinan, F Conley, M Molloy, AM Cox, C Scott, JM Brody, LC AF Parle-McDermott, A Mills, JL Kirke, PN O'Leary, VB Swanson, DA Pangilinan, F Conley, M Molloy, AM Cox, C Scott, JM Brody, LC TI Analysis of the MTHFR 1298A -> C and 677C -> T polymorphisms as risk factors for neural tube defects SO JOURNAL OF HUMAN GENETICS LA English DT Article DE MTHFR; A1298C; neural tube defects; C677T; linkage disequilibrium ID METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; LINKAGE DISEQUILIBRIUM; GERMAN POPULATION; COMMON MUTATION; GENETIC RISK; FOLATE; GENOTYPES; NTD; HOMOCYSTEINE AB The thermolabile variant (677TT) of methylenetetrahydrofolate reductase (MTHFR) is a known risk factor for neural tube defects (NTDs). The relationship between a second MTHFR polymorphism (1298A --> C) and NTD risk has been inconsistent between studies. We genotyped 276 complete NTD triads (mother, father and child affected with an NTD) and 256 controls for MTHFR 1298A --> C. Our findings do not support a role for the 1298A --> C polymorphism in NTDs (OR 0.85 (95% CI 0.49-1.47), p = 0.55), nor do we observe a combined effect with the 677C --> T polymorphism. C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. RP Parle-McDermott, A (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. OI Molloy, Anne/0000-0002-1688-9049; O'Leary, Valerie/0000-0003-1171-9830 NR 20 TC 41 Z9 49 U1 0 U2 2 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PY 2003 VL 48 IS 4 BP 190 EP 193 DI 10.1007/s10038-003-0008-4 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 674TP UT WOS:000182652300006 PM 12730722 ER PT J AU Hengel, RL Thaker, V Pavlick, MV Metcalf, JA Dennis, G Yang, J Lempicki, RA Sereti, I Lane, HC AF Hengel, RL Thaker, V Pavlick, MV Metcalf, JA Dennis, G Yang, J Lempicki, RA Sereti, I Lane, HC TI L-selectin (CD62L) expression distinguishes small resting memory CD4(+) T cells that preferentially respond to recall antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NODE HOMING RECEPTOR; LYMPHOCYTE RECIRCULATION; NAIVE; IMMUNODEFICIENCY; DIFFERENTIATION; INFECTION; PHENOTYPE; EFFECTOR; SUBSETS; HUMANS AB Naive CD4(+) T cells use L-selectin (CD62L) expression to facilitate immune surveillance. However, the reasons for its expression on a subset of memory CD4(+) T cells are unknown. We show that memory CD4(+) T cells expressing CD62L were smaller, proliferated well in response to tetanus toxoid, bad longer telomeres, and expressed genes and proteins consistent with immune surveillance function. Conversely, memory CD4(+) T cells lacking CD62L expression were larger, proliferated poorly in response to tetanus toxoid had shorter telomeres, and expressed genes and proteins consistent with effector function. These findings suggest that CD62L expression facilitates immune surveillance by programming CD4(+) T cell blood and lymph node recirculation, irrespective of naive or memory CD4(+) T cell phenotype. C1 NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Med, Div Infect Dis, Washington, DC 20053 USA. NIAID, Off Clin Director, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. RP Hengel, RL (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, 11B05,Bldg 10,9800 Rockville Pike, Bethesda, MD 20892 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 29 TC 66 Z9 68 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 28 EP 32 PG 5 WC Immunology SC Immunology GA 630KT UT WOS:000180106600006 PM 12496379 ER PT J AU Wu, JM Metzt, C Xu, XL Abe, R Gibson, AW Edberg, JC Cooke, J Xie, FL Cooper, GS Kimberly, TP AF Wu, JM Metzt, C Xu, XL Abe, R Gibson, AW Edberg, JC Cooke, J Xie, FL Cooper, GS Kimberly, TP TI A novel polymorphic CAAT/enhancer-binding protein beta element in the FasL gene promoter alters Fas ligand expression: A candidate background gene in African American systemic lupus erythematosus patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; APOPTOTIC CELLS; LYMPHOPROLIFERATIVE SYNDROME; REVISED CRITERIA; DEFICIENT MICE; MACROPHAGES; ANTIGEN; C/EBP; CD95; DISEASE AB A single-nucleotide polymorphism (SNP), identified at nucleotide position -844 in the 5' promoter of the FasL gene, lies within a putative binding motif for CAAT/enhancer-binding protein beta (C/EBPbeta). Electrophoretic mobility shift and supershift assays confirmed that this element binds specifically to C/EBPbeta and demonstrated that the two alleles of this element have different affinities for C/EBPbeta. In luciferase reporter assays, the -844C genotype had twice the basal activity of the -844T construct, and basal expression of Fas ligand (FasL) on peripheral blood fibrocytes was also significantly higher in -844C than in -844T homozygous donors. FasL is located on human chromosome 1q23, a region that shows linkage to the systemic lupus autoimmune phenotype. Analysis of 211 African American systemic lupus erythematosus patients revealed enrichment of the -844C homozygous genotype in these systemic lupus erythematosus patients compared with 150 ethnically matched normal controls (p = 0.024). The -844C homozygous genotype may lead to the increased expression of FasL, to altered FasL-mediated signaling in lymphocytes, and to enhanced risk for autoimmunity. This functionally significant SNP demonstrates the potential importance of SNPs in regulatory regions and suggests that differences in the regulation of FasL expression may contribute to the development of the autoimmune phenotype. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Picower Inst Med Res, Med Biochem Lab, Manhasset, NY 11030 USA. Rush Presbyterian St Lukes Med Ctr, Dept Gen Surg, Chicago, IL 60612 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Kimberly, TP (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, 429 Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. FU NIAMS NIH HHS [R01 AR33062, P01 AR49084, P30 AR048311, P30 AR48311, P50 AR45231, T32 AR07350] NR 40 TC 153 Z9 163 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 132 EP 138 PG 7 WC Immunology SC Immunology GA 630KT UT WOS:000180106600019 PM 12496392 ER PT J AU Hathcock, KS Kaech, SM Ahmed, R Hodes, RJ AF Hathcock, KS Kaech, SM Ahmed, R Hodes, RJ TI Induction of telomerase activity and maintenance of telomere length in virus-specific effector and memory CD8(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; CUTTING EDGE; EXPRESSION; MICE; PERSISTENCE; SENESCENCE; MECHANISM; INFECTION; MOUSE; NAIVE AB Acute viral infections induce extensive proliferation and differentiation of virus-specific CD8(+) T cells. One mechanism reported to regulate the proliferative capacity of activated lymphocytes is mediated by the effect of telomerase in maintaining the length of telomeres in proliferating cells. We examined the regulation of telomerase activity and telomere length in naive CD8(+) T cells and in virus-specific CD8(+) T cells isolated from mice infected with lymphocytic choriomeningitis virus. These studies reveal that, compared with naive CD8(+) T cells, which express little or no telomerase activity, Ag-specific effector and long-lived memory CD8(+) T cells express high levels of telomerase activity. Despite the extensive clonal expansion that occurs during acute lymphocytic choriomeningitis virus infection, telomere length is maintained in both effector and memory CD8(+) T cells. These results suggest that induction of telomerase activity in Ag-specific effector and memory CD8(+) T cells is important for the extensive clonal expansion of both primary and secondary effector cells and for the maintenance and longevity of the memory CD8(+) T cell population. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Hathcock, KS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B10,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI30048] NR 29 TC 36 Z9 36 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 147 EP 152 PG 6 WC Immunology SC Immunology GA 630KT UT WOS:000180106600021 PM 12496394 ER PT J AU Kelly, J Spolski, R Imada, K Bollenbacher, J Lee, S Leonard, WJ AF Kelly, J Spolski, R Imada, K Bollenbacher, J Lee, S Leonard, WJ TI A role for Stat5 in CD8(+) T cell homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-GAMMA CHAIN; MEMORY-PHENOTYPE; IN-VIVO; TRANSGENIC MICE; NATURAL-KILLER; IL-2 RECEPTOR; LYMPHOID HOMEOSTASIS; GENE-REGULATION; ALPHA-CHAIN; PROLIFERATION AB Cytokine signals are known to contribute to CD8(+) memory T cell homeostasis, but an exact understanding of the mechanism(s) has remained elusive. We have now investigated the role of Stat5 proteins in this process. Whereas Stat5a and Stat5b KO mice have decreased numbers of CD8(+) T cells, Stat5-transgenic mice have an increased number of these cells. Stat5b-transgenic mice exhibit increased Ag-induced cell death of CD4(+) T cells and augmented proliferation and Bcl-2 expression in CD8(+) T cells, providing a basis for this finding. Moreover, CD8(+) memory T cells are substantially affected by Stat5 levels. These findings identify Stat5 proteins as critical signaling mediators used by cytokines to regulate CD8(+) T cell homeostasis. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 52 TC 51 Z9 52 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 210 EP 217 PG 8 WC Immunology SC Immunology GA 630KT UT WOS:000180106600029 PM 12496402 ER PT J AU Bronte, V Serafini, P De Santo, C Marigo, I Tosello, V Mazzoni, A Segal, DM Staib, C Lowel, M Sutter, G Colombo, MP Zanovello, P AF Bronte, V Serafini, P De Santo, C Marigo, I Tosello, V Mazzoni, A Segal, DM Staib, C Lowel, M Sutter, G Colombo, MP Zanovello, P TI IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; COLONY-STIMULATING FACTOR; GR-1(+) MYELOID CELLS; DENDRITIC CELLS; L-ARGININE; MACROPHAGE ARGINASE; MURINE MACROPHAGES; APOPTOTIC DEATH; IN-VIVO; ACTIVATION AB We previously demonstrated that a specialized subset of immature myeloid cells migrate to lymphoid organs as a result of tumor growth or immune stress, where they suppress B and T cell responses to Ags. Although NO was required for suppression of mitogen activation of T cells by myeloid suppressor cells (MSC), it was not required for suppression of allogenic responses. In this study, we describe a novel mechanism used by MSC to block T cell proliferation and CTL generation in response to alloantigen, which is mediated by the enzyme arginase 1 (Arg1). We show that Arg1 increases superoxide production in myeloid cells through a pathway that likely utilizes the reductase domain of inducible NO synthase (iNOS), and that superoxide is required for Arg1-dependent suppression of T cell function. Arg1 is induced by IL-4 in freshly isolated MSC or cloned MSC lines, and is therefore up-regulated by activated Th2, but not Th1, cells. In contrast, iNOS is induced by IFN-gamma and Th1 cells. Because Arg1 and iNOS share L-arginine as a common substrate, our results indicate that L-arginine metabolism in myeloid cells is a potential target for selective intervention in reversing myeloid-induced dysfunction in tumor-bearing hosts. C1 Univ Padua, Dept Oncol & Surg Sci, Oncol Sect, I-35128 Padua, Italy. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. GSF, Natl Res Ctr Environm & Hlth, Inst Mol Virol, Munich, Germany. Ist Nazl Tumori, Dept Expt Oncol, Immunotherapy & Gene Therapy Unit, I-20133 Milan, Italy. RP Bronte, V (reprint author), Univ Padua, Dept Oncol & Surg Sci, Oncol Sect, Via Gattamelata 64, I-35128 Padua, Italy. RI Serafini, Paolo/C-8195-2012; Bronte, Vincenzo/K-7902-2016; OI Serafini, Paolo/0000-0002-3651-9176; Bronte, Vincenzo/0000-0002-3741-5141; Colombo, Mario Paolo/0000-0003-0042-7955; Tosello, Valeria/0000-0001-9560-340X NR 37 TC 255 Z9 268 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 270 EP 278 PG 9 WC Immunology SC Immunology GA 630KT UT WOS:000180106600036 PM 12496409 ER PT J AU Barber, DF Long, EO AF Barber, DF Long, EO TI Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; DROSOPHILA-MELANOGASTER CELLS; ANTIVIRAL DEFENSE; CROSS-LINKING; ACTIVATION; RECEPTORS; PARTICIPATION; CYTOLYSIS; BINDING; CD2 AB The beta(2) integrin LFA-1 (CD11a/CD18) mediates adhesion of lymphocytes to cells expressing ICAM. The strength of this adhesion is regulated by different signals delivered by cytokines and chemokines, and by the TCR in the case of T cells. To determine the receptor-ligand interactions required for adhesion of resting NK cells, Drosophila cells expressing different combinations of ligands of human NK cell receptors were generated. Expression of ICAM-1 alone was sufficient for an adhesion of resting NK cells that was sensitive to inhibitors of src family kinase and of phosphatidylinositol 3-kinase. Binding of resting NK cells to solid-phase ICAM-1 showed similar signaling requirements. A pulse of either IL-2 or IL-15 to resting NK cells resulted in strongly enhanced, actin-dependent adhesion to insect cells expressing ICAM-1 alone. Coexpression of either LFA-3 (CD58) or CD48 with ICAM-1 resulted in strong adhesion by resting NK cells, even in the absence of cytokines. Therefore, receptors for LFA-3 and CD48 on resting NK cells strengthen the adhesion mediated by LFA-1. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Barber, Domingo/G-1257-2010; Long, Eric/G-5475-2011 OI Barber, Domingo/0000-0001-8824-5405; Long, Eric/0000-0002-7793-3728 NR 25 TC 66 Z9 70 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 294 EP 299 PG 6 WC Immunology SC Immunology GA 630KT UT WOS:000180106600039 PM 12496412 ER PT J AU Buslepp, J Kerry, SE Loftus, D Frelinger, JA Appella, E Collins, EJ AF Buslepp, J Kerry, SE Loftus, D Frelinger, JA Appella, E Collins, EJ TI High affinity xenoreactive TCR : MHC interaction recruits CD8 in absence of binding to MHC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; CLASS-I MOLECULES; PROTEIN-TYROSINE KINASES; CORECEPTOR FUNCTION; ALPHA-3 DOMAIN; MHC/PEPTIDE COMPLEXES; CYTOPLASMIC DOMAINS; POSITIVE SELECTION; CRYSTAL-STRUCTURE; ANTIGEN AB The TCR from a xenoreactive murine cytotoxic T lymphocyte clone, AHIII 12.2, recognizes murine H-2D(b) complexed with peptide p1058 (FAPGFFPYL) as well as human HLA-A2.1 complexed with human self-peptide p1049 (ALWGFFPVL). To understand more about T cell biology and cross-reactivity, the ectodomains of the AHIII 12.2 TCR have been produced in E. coli as inclusion bodies and the protein folded to its native conformation. Flow cytometric and surface plasmon resonance analyses indicate that human p1049/A2 has a significantly greater affinity for the murine AHIII 12.2 TCR than does murine p1058/D-b. Yet, T cell binding and cytolytic activity are independent of CD8 when stimulated with human p1049/A2 as demonstrated with anti-CD8 Abs that block CD8 association with MHC. Even in the absence of direct CD8 binding, stimulation of AHIII 12.2 T cells with "CD8-independent" p1049/A2 produces p56(lck) activation and calcium flux. Confocal fluorescence microscopy and fluorescence resonance energy transfer flow cytometry demonstrate CD8 is recruited to the site of TCR:peptide MHC binding. Taken together, these results indicate that there exists another mechanism for recruitment of CD8 during high affinity TCR:peptide MHC engagement. C1 Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Collins, EJ (reprint author), Univ N Carolina, Dept Microbiol & Immunol, CB 7290,804 ME Jones Bldg, Chapel Hill, NC 27599 USA. FU NIGMS NIH HHS [GM67143]; PHS HHS [007273] NR 66 TC 23 Z9 23 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 373 EP 383 PG 11 WC Immunology SC Immunology GA 630KT UT WOS:000180106600049 PM 12496422 ER PT J AU Dobrovolskaia, MA Medvedev, AE Thomas, KE Cuesta, N Toshchakov, V Ren, TB Cody, MJ Michalek, SM Rice, NR Vogel, SN AF Dobrovolskaia, MA Medvedev, AE Thomas, KE Cuesta, N Toshchakov, V Ren, TB Cody, MJ Michalek, SM Rice, NR Vogel, SN TI Induction of in vitro reprogramming by toll-like receptor (TLR)2 and TLR4 agonists in murine macrophages: Effects of TLR "homotolerance" versus "heterotolerance" on NF-kappa B signaling pathway components SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTOXIN TOLERANCE; GENE-EXPRESSION; PROTEIN-KINASE; LIPOPOLYSACCHARIDE-TOLERANCE; LIPOTEICHOIC ACID; CROSS-TOLERANCE; CUTTING EDGE; IN-VIVO; CELLS; ALPHA AB In this study, tolerance induction by preexposure of murine macrophages to Toll-like receptor (TLR)2 and TLR4 agonists was revisited, focusing on the major signaling components associated with NF-kappaB activation. Pretreatment of macrophages with a pure TLR4 agonist (protein-free Escherichia coli (Ec) LPS) or with TLR2 agonists (Porphyromonas gingivalis LPS or synthetic lipoprotein Pam3Cys) led to suppression of TNF-alpha secretion, IL-1R-associated kinase-1. and IkappaB kinase (IKK) kinase activities, c-jun N-terminal kinase, and extracellular signal-regulated kinase phosphorylation, and to suppression of NF-kappaB DNA binding and transactivation upon challenge with the same agonist (TLR4 or TLR2 "homototerance," respectively). Despite inhibited NF-kappaB DNA binding, increased levels of nuclear NF-kappaB were detected in agonist-pretreated macrophages. For all the intermediate signaling elements, heterotolerance was weaker than TLR4 or TLR2 homotolerance with the exception of IKK kinase activity. IKK kinase activity was unperturbed in heterotolerance. TNF-alpha secretion was also suppressed in P. gingivalis LPS-pretreated, Ec LPS-challenged cells, but not vice versa, while Pam3Cys and Ec LPS did not induce a state of cross-tolerance at the level of TNF-alpha. Experiments designed to elucidate novel mechanisms of NF-kappaB inhibition in tolerized cells revealed the potential contribution of IkappaBepsilon and IkappaBxi inhibitory proteins and the necessity of TLR4 engagement for induction of tolerance to Toll receptor-IL-1R domain-containing adapter protein/MyD88-adapter-like-dependent gene expression. Collectively, these data demonstrate that induction of homotolerance affects a broader spectrum of signaling components than in heterotolerance, with selective modulation of specific elements within the NF-kappaB signaling pathway. C1 Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Oral Biol, Birmingham, AL 35294 USA. Natl Canc Inst, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Vogel, SN (reprint author), Univ Maryland, Dept Microbiol & Immunol, 655 Baltimore St 13-009, Baltimore, MD 21201 USA. RI Cuesta, Natalia/C-1358-2012; Toshchakov, Vladimir/C-2798-2014; Cuesta, Natalia/J-7761-2015 OI Toshchakov, Vladimir/0000-0002-7942-2294; Cuesta, Natalia/0000-0003-0809-2934 FU NIAID NIH HHS [AI-44936, AI-18797]; NIDCR NIH HHS [DE-08182, DE-09081, DE14215] NR 73 TC 222 Z9 230 U1 1 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2003 VL 170 IS 1 BP 508 EP 519 PG 12 WC Immunology SC Immunology GA 630KT UT WOS:000180106600065 PM 12496438 ER PT J AU Javia, LR Rosenberg, SA AF Javia, LR Rosenberg, SA TI CD4(+)CD25(+) suppressor lymphocytes in the circulation of patients immunized against melanoma antigens SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CD4(+)CD25(+) suppressor lymphocytes; immunotherapy; interleukin-2; metastatic melanoma ID REGULATORY T-CELLS; IMMUNOLOGICAL SELF-TOLERANCE; IN-VITRO; IMMUNOREGULATORY CELLS; PERIPHERAL-BLOOD; ACTIVATION; IMMUNOTHERAPY; POPULATION; REJECTION; INDUCTION AB Murine studies have suggested that a population of CD4(+) T cells expressing the alpha chain of the interleukin (IL)-2 receptor (CD25(+)) are phenotypically anergic in response to T cell receptor stimulation and can suppress the function of CD4(+) and CD8(+) T cells. Recent studies of peripheral lymphocytes from healthy human volunteers have identified a similar population, although little is known about the presence and activity of these cells in patients with cancer and their possible impact on anticancer immunization strategies. Thus, the authors have undertaken these studies in patients with metastatic melanoma undergoing immunizations with known melanoma antigens. CD4(+)CD25(+), CD4(+)CD25(-), and a 1: 1 ratio of these isolated T cells were stimulated with soluble anti-CD3 antibody in the presence of irradiated T cell-depleted PBMCs, and proliferation was assessed by measuring [H-3]thymidine incorporation. In 13 patients, isolated CD4(+)CD25(+) T cells proliferated 68% ( 5.8%) less than separately cultured CD4'CD25- T cells. Moreover, CD4(+)CD25(+) T cells suppressed the proliferation of an equal number of cocultured CD4(+)CD25(+) T cells in 11 of 13 patients by an average of 60% (4.9%). Suppression was not seen at day three of culture and became apparent at days five through nine. The degree of suppression was proportional to the numbers of CD4(+)CD25(+) T cells. Addition of high-dose IL-2 reversed the hypoproliferative phenotype of the CD4(+)CD25(+) T cells and abrogated their suppressive function. These studies demonstrate that anergic and functionally suppressive CD4(+)CD25(+) T cells exist in patients with melanoma undergoing tumor antigen immunization and thus may play a role in modifying the magnitude of the T cell response to immunization. C1 NCI, Howard Hughes Med Inst, NIH, Hlth Res Programs,Surg Branch, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 31 TC 91 Z9 100 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2003 VL 26 IS 1 BP 85 EP 93 DI 10.1097/00002371-200301000-00009 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 646GM UT WOS:000181027300009 PM 12514432 ER PT J AU Biggar, RJ Engels, EA Whitby, D Kedes, DH Goedert, JJ AF Biggar, RJ Engels, EA Whitby, D Kedes, DH Goedert, JJ TI Antibody reactivity to latent and lytic antigens to human herpesvirus-8 in longitudinally followed homosexual men SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; IMMUNODEFICIENCY-VIRUS TYPE-1; KAPOSIS-SARCOMA; DNA-SEQUENCES; HIV-INFECTION; RISK-FACTORS; HUMAN-HERPESVIRUS-8; INDIVIDUALS; PREVALENCE; ASSAYS AB Tests for human herpesvirus-8 (HHV-8) often disagree on which individuals are infected. To evaluate HHV-8 antibody changes over many years, 245 homosexual men enrolled in a prospective study between 1982 and 1999 were studied. Samples collected annually were evaluated by immunofluorescence to HHV-8 latent nuclear antigen and by an ELISA for antibody against the HHV-8 lytic antigen K8.1. When positive, samples from most subjects were persistently reactive in both assays. Titers to both lytic and latent antibodies increased for many years, usually in parallel, and were higher in human immunodeficiency virus-infected men. The increasing titers and expanding epitope recognition suggest ongoing, low-grade replication of HHV-8. Use of multiple assays is important in determining prevalence in asymptomatic populations. Because persons with more advanced infections have higher antibody titers, they are easier to detect, which may skew our understanding of the epidemiology of HHV-8. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. NCI, Viral Epidemiol Lab, SAIC Frederick, Frederick, MD 21701 USA. Univ Virginia Htlh Syst, Dept Microbiol, Charlottesville, VA USA. Univ Virginia Htlh Syst, Dept Internal Med, Charlottesville, VA USA. RP Biggar, RJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 8014, Bethesda, MD 20852 USA. FU NCI NIH HHS [N01-CO-12400] NR 25 TC 33 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2003 VL 187 IS 1 BP 12 EP 18 DI 10.1086/345866 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 625GZ UT WOS:000179809900003 PM 12508141 ER PT J AU Klion, AD Vijaykumar, A Oei, T Martin, B Nutman, TB AF Klion, AD Vijaykumar, A Oei, T Martin, B Nutman, TB TI Serum immunoglobulin G4 antibodies to the recombinant antigen, Ll-SXP-1, are highly specific for Loa loa infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 27-DEC 02, 1999 CL WASHINGTON, D.C. SP Amer Soc Trop Med & Hyg ID WUCHERERIA-BANCROFTI; LYMPHATIC FILARIASIS; ENDEMIC REGIONS; FOLLOW-UP; LOIASIS; DIAGNOSIS; IGG4; ONCHOCERCIASIS; RESPONSES; AREA AB The clinical manifestations and geographic distribution of loiasis overlap with those of other human filarial parasites, presenting challenges in the specific diagnosis of loiasis that may lead to delays in appropriate therapy. A recombinant antigen (Ll-SXP-1), preferentially recognized by serum samples from experimentally infected rhesus monkeys, was identified from a Loa loa L3 cDNA library. IgG4 antibody reactivity to purified Ll-SXP-1 was assessed by means of ELISA, using serum samples from patients with loiasis, lymphatic filariasis, onchocerciasis, mansonellosis, or other helminthiases and healthy control subjects. The assay was 56% sensitive and 98% specific for loiasis. Antibody reactivity was detectable before microfilaremia in experimentally infected rhesus monkeys and declined (but did not disappear) after diethylcarbamazine therapy in infected patients. IgG4 antibodies to recombinant Ll-SXP-1 are a highly specific marker of L. loa infection and may be useful for the diagnostic evaluation of persons with filariasis of unclear etiology. C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), NIH, Parasit Dis Lab, Bldg 4,Rm 126, Bethesda, MD 20892 USA. OI Klion, Amy/0000-0002-4986-5326 NR 25 TC 28 Z9 28 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2003 VL 187 IS 1 BP 128 EP 133 DI 10.1086/345873 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 625GZ UT WOS:000179809900018 PM 12508156 ER PT J AU Little, RF Mercad-Galindez, F Staskus, K Whitby, D Aoki, Y Humphrey, R Pluda, JM Marshall, V Walters, M Welles, L Rodriguez-Chavez, IR Pittaluga, S Tosato, G Yarchoan, R AF Little, RF Mercad-Galindez, F Staskus, K Whitby, D Aoki, Y Humphrey, R Pluda, JM Marshall, V Walters, M Welles, L Rodriguez-Chavez, IR Pittaluga, S Tosato, G Yarchoan, R TI A pilot study of cidofovir in patients with Kaposi sarcoma SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th International AIDS Malignancy Conference CY APR 23-25, 2001 CL BETHEDSA, MARYLAND ID AIDS; HUMAN-HERPESVIRUS-8; HERPESVIRUS; SENSITIVITY; REPLICATION; EXPRESSION; DRUGS; CELLS AB A clinical trial was conducted to test the activity of cidofovir (CDV), a drug with in vitro activity against Kaposi sarcoma (KS)-associated herpesvirus (KSHV), in KS. Five patients with human immunodeficiency virus-associated KS (4 receiving antiretroviral therapy) and 2 patients with classical KS were administered CDV (5 mg/kg/dose) weekly for 2 weeks and then every other week. All 7 patients had progression of their KS at a median of 8.1 weeks (range, 5-27 weeks). Skin biopsy specimens of KS lesions showed no change in expression of latent or early lytic genes, but, in the 1 assessable patient, there was decreased expression of a late lytic gene. There was no decrease in the virus load of KSHV in peripheral blood mononuclear cells. This study does not provide proof of principle for the treatment of KS with CDV. However, it remains possible that antiherpesvirus therapy can be developed for herpes-induced tumors. C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Viral Epidemiol Lab, Frederick, MD 21701 USA. Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. RP Yarchoan, R (reprint author), NIH, Bldg 10,Rm 10S255,MSC 1868,10 Ctr Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-12400] NR 15 TC 47 Z9 53 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2003 VL 187 IS 1 BP 149 EP 153 DI 10.1086/346159 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 625GZ UT WOS:000179809900022 PM 12508160 ER PT J AU Li, T Glushakova, S Zimmerberg, J AF Li, T Glushakova, S Zimmerberg, J TI A new method for culturing Plasmodium falciparum shows replication at the highest erythrocyte densities SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HOLLOW-FIBER BIOREACTOR; MALARIA; CELLS AB Plasmodium falciparum replicates poorly in erythrocyte densities greater than a hematocrit of 20%. A new method to culture the major malaria parasite was developed by using a hollow fiber bioreactor that preserves healthy erythrocytes at hematocrit up to 100%. P. falciparum replicated equally well at all densities studied. This method proved advantageous for large-scale preparation of parasitized erythrocytes (and potentially immunogens thereof), because high yields (similar to10(10) in 4 days) could be prepared with less cost and labor. Concomitantly, secreted proteins were concentrated by molecular sieving during culture, perhaps contributing to the parasitemic limit of 8%-12% with the 3D7 strain. The finding that P. falciparum can replicate at packed erythrocyte densities suggests that this system may be useful for study of the pathogenesis of fatal cerebral malaria, of which one feature is densely packed blood cells in brain microvasculature. C1 NICHHD, NASA NIH Ctr Dimens Tissue Culture 3, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, NASA NIH Ctr Dimens Tissue Culture 3, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 10D14,10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 8 Z9 10 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2003 VL 187 IS 1 BP 159 EP 162 DI 10.1086/345876 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 625GZ UT WOS:000179809900024 PM 12508162 ER PT J AU Ries, M Mengel, E Kutschke, G Kim, KS Birklein, F Krummenauer, F Beck, M AF Ries, M Mengel, E Kutschke, G Kim, KS Birklein, F Krummenauer, F Beck, M TI Use of gabapentin to reduce chronic neuropathic pain in Fabry disease SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID THERAPY AB The effect of the anticonvulsant gabapentin on neuropathic pain was studied in six male patients with Fabry disease, aged 15-45 years. After 4 weeks of treatment, pain, as measured using the Brief Pain Inventory, was decreased compared with baseline. Treatment was generally well tolerated. This study indicates that gabapentin should be considered as a treatment option for the neuropathic pain of Fabry disease. C1 Univ Mainz, Ctr Lysosomal Storage Disorders, D-6500 Mainz, Germany. Univ Mainz, Childrens Hosp, D-6500 Mainz, Germany. Univ Mainz, Neurol Clin, D-6500 Mainz, Germany. Univ Mainz, Dept Med Biometry Epidemiol & Informat, D-6500 Mainz, Germany. RP Ries, M (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, 10 Ctr Dr,Room 3D03, Bethesda, MD 20892 USA. NR 3 TC 39 Z9 41 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2003 VL 26 IS 4 BP 413 EP 414 DI 10.1023/A:1025127723729 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 711JU UT WOS:000184736500013 PM 12971431 ER PT J AU Mudd, SH Tangerman, A Stabler, SP Allen, RH Wagner, C Zeisel, SH Levy, HL AF Mudd, SH Tangerman, A Stabler, SP Allen, RH Wagner, C Zeisel, SH Levy, HL TI Maternal methionine adenosyltransferase I/III deficiency: Reproductive outcomes in a woman with four pregnancies SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID ISOLATED PERSISTENT HYPERMETHIONINEMIA; CHROMATOGRAPHY MASS-SPECTROMETRY; DOMINANT INHERITANCE; S-ADENOSYLMETHIONINE; GAS-CHROMATOGRAPHY; TOTAL HOMOCYSTEINE; FOLATE-DEFICIENCY; INBORN-ERRORS; CHOLINE; SERUM AB Four pregnancies in a women with moderately severe deficiency of methionine adenosyltransferase I/III (MAT I/III) activity are reported. She is an apparent homozygote for a point mutation in MAT1A, the gene that encodes the catalytically active subunit of MAT I/III. This mutation reduces the activity of her expressed enzyme to some 11% of wild-type. She was the first such individual identified in the United States, and these are the first pregnancies known in anyone with this extent of MAT I/III deficiency. No adverse effects were noted in the mother. Three normal babies resulted, but fetal arrest was detected in one embryo at 10-11 weeks gestation. Plasma methionine concentrations remained virtually constant at their elevated levels of 300-350 mumol/L throughout the pregnancies. Plasma free choline was below the reference range. In view of the evidence that maternal choline delivery to the fetus is important for brain development, it was suggested the patient ingest two eggs daily from gestation week 17. Plasma choline and phosphatidylcholine tended to rise during such supplementation. Plasma cystathionine concentrations rose progressively to far above normal during these pregnancies, but not during pregnancies in control women. This may be explained by delivery of excessive methionine to the fetus, with consequent increased cystathionine synthesis by fetal tissues. Because fetal tissues lack gamma-cystathionase, presumably cystathionine accumulated abnormally in the fetus and was transferred in abnormal amounts back to the mother. Plasma and urinary concentrations of methionine transamination metabolites rose during pregnancy for reasons that remain obscure. C1 NIMH, DIRP, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Med Ctr Nijmegen, Div Gastroenterol & Hepatol, Nijmegen, Netherlands. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Mudd, SH (reprint author), NIMH, DIRP, Mol Biol Lab, Bldg 36,Room IB-08,36 Convent Dr MSC 4034, Bethesda, MD 20892 USA. EM shm@codon.nih.gov FU NCRR NIH HHS [RR00046]; NIA NIH HHS [AG09523]; NIDDK NIH HHS [DK56350, DK55865] NR 43 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2003 VL 26 IS 5 BP 443 EP 458 DI 10.1023/A:1025121326959 PG 16 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 710QL UT WOS:000184690900004 PM 14518826 ER PT J AU Augoustides-Savvopoulou, P Luka, Z Karyda, S Stabler, SP Allen, RH Patsiaoura, K Wagner, C Mudd, SH AF Augoustides-Savvopoulou, P Luka, Z Karyda, S Stabler, SP Allen, RH Patsiaoura, K Wagner, C Mudd, SH TI Glycine N-methyltransferase deficiency: A new patient with a novel mutation SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID CYSTATHIONINE BETA-SYNTHASE; FOLATE-BINDING-PROTEIN; S-ADENOSYLMETHIONINE; TOTAL HOMOCYSTEINE; RAT-LIVER; PLASMA HOMOCYSTEINE; MASS-SPECTROMETRY; PURIFICATION; METHIONINE; INHIBITION AB We report studies of a Greek boy of gypsy origin that show that he has severe deficiency of glycine N- methyltransferase ( GNMT) activity due to apparent homozygosity for a novel mutation in the gene encoding this enzyme that changes asparagine- 140 to serine. At age 2 years he was found to have mildly elevated serum liver transaminases that have persisted to his present age of 5 years. At age 4 years, hypermethioninaemia was discovered. Plasma methionine concentrations have ranged from 508 to 1049 mumol/ L. Several known causes of hypermethioninaemia were ruled out by studies of plasma metabolites: tyrosinaemia type I by a normal plasma tyrosine and urine succinylacetone; cystathionine beta- synthase deficiency by total homocysteine of 9.4 - 12.1 mumol/ L; methionine adenosyltransferase I/ III deficiency by S- adenosylmethionine ( AdoMet) levels elevated to 1643 - 2222 nmol/ L; and S- adenosylhomocysteine ( AdoHcy) hydrolase deficiency by normal AdoHcy levels. A normal plasma N- methylglycine concentration in spite of elevated AdoMet strongly suggested GNMT deficiency. Molecular genetic studies identified a missense mutation in the coding region of the boy's GNMT gene, which, upon expression, retained only barely detectable catalytic activity. The mild hepatitis- like manifestations in this boy are similar to those in the only two previously reported children with GNMT deficiency, strengthening the likelihood of a causative association. Although his deficiency of GNMT activity may well be more extreme, his metabolic abnormalities are not strikingly greater. Also discussed is the metabolic role of GNMT; several additional metabolite abnormalities found in these patients; and remaining questions about human GNMT deficiency, such as the long- term prognosis, whether other individuals with this defect are currently going undetected, and means to search for such persons. C1 NIMH, DIRP, LMB, Bethesda, MD 20892 USA. Hippocrat Gen Hosp, Pediat Biochem Metab Lab, Thessaloniki, Greece. Hippocrat Gen Hosp, Dept Pediat, Thessaloniki, Greece. Hippocrat Gen Hosp, Dept Pathol, Thessaloniki, Greece. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO USA. RP Mudd, SH (reprint author), NIMH, DIRP, LMB, Bldg 36,Room 1B-08,36 Convent Dr 4034, Bethesda, MD 20892 USA. NR 46 TC 52 Z9 52 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2003 VL 26 IS 8 BP 745 EP 759 DI 10.1023/B:BOLI.0000009978.17777.33 PG 15 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 757AG UT WOS:000187517500003 PM 14739680 ER PT J AU Miranda, KM Nims, RW Thomasa, DD Espey, MG Citrin, D Bartberger, MD Paolocci, N Fukuto, JM Feelisch, M Wink, DA AF Miranda, KM Nims, RW Thomasa, DD Espey, MG Citrin, D Bartberger, MD Paolocci, N Fukuto, JM Feelisch, M Wink, DA TI Comparison of the reactivity of nitric oxide and nitroxyl with heme proteins - A chemical discussion of the differential biological effects of these redox related products of NOS SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE nitric oxide; nitroxyl; Angeli's salt; heme; horseradish peroxidase; myoglobin; hemoglobin ID SOLUBLE GUANYLATE-CYCLASE; AQUEOUS-SOLUTION; L-ARGININE; SUPEROXIDE-DISMUTASE; NITROSYL HYDRIDE; NMDA RECEPTOR; SYNTHASE; OXIDATION; ANION; DISSOCIATION AB Investigations on the biological effects of nitric oxide (NO) derived from nitric oxide synthase (NOS) have led to an explosion in biomedical research over the last decade. The chemistry of this diatomic radical is key to its biological effects. Recently, nitroxyl (HNO/NO-) has been proposed to be another important constituent of NO biology. However, these redox siblings often exhibit orthogonal behavior in physiological and cellular responses. We therefore explored the chemistry of NO and HNO with heme proteins in different redox states and observed that HNO favors reaction with ferric heme while NO favors ferrous, consistent with previous reports. Further results show that HNO and NO were equally effective in inhibiting cytochrome P450 activity, which involves ferric and ferrous complexes. The differential chemical behavior of NO and HNO toward heme proteins provides insight into mechanisms of activity that not only helps explain some of the opposing effects observed in NOS-mediated events, but offers a unique control mechanism for the biological action of NO. Published by Elsevier Science Inc. C1 NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Biomed Engn, Baltimore, MD 21287 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. RP Wink, DA (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009; Feelisch, Martin/C-3042-2008 OI Feelisch, Martin/0000-0003-2320-1158 NR 77 TC 91 Z9 94 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD JAN 1 PY 2003 VL 93 IS 1-2 BP 52 EP 60 AR PII S0162-0134(02)00498-1 DI 10.1016/S0162-0134(02)00498-1 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 641BT UT WOS:000180724800012 PM 12538052 ER PT J AU Katz, SI Bergstresser, P Eaglstein, WH AF Katz, SI Bergstresser, P Eaglstein, WH TI Harvey Blank, 1918-2001 - In memorium SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Biographical-Item C1 NIAMSD, Bethesda, MD 20892 USA. Univ Texas, SW Med Sch, Dept Dermatol, Dallas, TX 75390 USA. Univ Miami, Sch Med, Coral Gables, FL 33124 USA. RP Katz, SI (reprint author), NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2003 VL 120 IS 1 BP 2 EP 3 PG 2 WC Dermatology SC Dermatology GA 635TP UT WOS:000180415700002 ER PT J AU Kon, A Takeda, H Sasaki, H Yoneda, K Nomura, K Ahvazi, B Steinert, PM Hanada, K Hashimoto, I AF Kon, A Takeda, H Sasaki, H Yoneda, K Nomura, K Ahvazi, B Steinert, PM Hanada, K Hashimoto, I TI Novel transglutaminase 1 gene mutations (R348X/Y365D) in a Japanese family with lamellar ichthyosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID CORNIFIED CELL-ENVELOPE; KERATINOCYTE TRANSGLUTAMINASE; RECESSIVE ICHTHYOSIS; DIFFERENTIATION; HETEROGENEITY C1 Hirosaki Univ, Sch Med, Dept Dermatol, Hirosaki, Aomori 0368562, Japan. Akita Univ, Sch Med, Dept Dermatol, Akita 010, Japan. Aomori Prefectural Cent Hosp, Dept Dermatol, Aomori, Japan. NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. RP Kon, A (reprint author), Hirosaki Univ, Sch Med, Dept Dermatol, 5 Zaifu Cho, Hirosaki, Aomori 0368562, Japan. NR 19 TC 2 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2003 VL 120 IS 1 BP 170 EP 172 DI 10.1046/j.1523-1747.2003.19522.x PG 3 WC Dermatology SC Dermatology GA 635TP UT WOS:000180415700028 PM 12535215 ER PT J AU Katoch-Rouse, R Horti, AG AF Katoch-Rouse, R Horti, AG TI Synthesis of N-(piperidin-1-yl)-5-(4-methoxyphenyl)-1-(2-chlorophenyl)-4-[F-18]fluoro -1H-pyrazole-3-carboxamide by nucleophilic [F-18] fluorination: a PET radiotracer for studying CB1 cannabinoid receptors SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE positron emission tomography; cannabinoid receptors; radiosynthesis; F-18; nucleophilic radiofluorination ID RADIOLIGAND; SR144385 AB The feasibility of nucleophilic displacement of bromide in the 4-bromopyrazole ring with [F-18]fluoride has been demonstrated by the synthesis of two radiolabeled compounds: N-(piperidin-1-yl)-5-(4-methoxyphenyl)-1-(2-chlorophenyl)-4-[F-18]fluoro-1H-pyrazole-3-carboxamide, ([F-18] NIDA-42033) 1b and 1-(2-chlorophenyl)-4-[F-18]fluoro-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid, ethyl ester 4. The radiochemical yields were in the range of 1-6%. [F-18]NIDA-42033, a potential radiotracer for the study of CB, cannabinoid receptors in the animal brain by positron emission tomography, has been synthesized in sufficient quantities with specific radioactivity greater than 2500 mCi/mumol and radiochemical purity > 95%. Copyright (C) 2002 John Wiley Sons, Ltd. C1 NIDR, IRP, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. RP Horti, AG (reprint author), NIDR, IRP, Neuroimaging Res Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ahorti@intra.nida.nih.gov NR 10 TC 17 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JAN PY 2003 VL 46 IS 1 BP 93 EP 98 DI 10.1002/jlcr.647 PG 6 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 640HB UT WOS:000180681700007 ER PT J AU Wang, P Sun, SH Silver, PB Chan, CC Agarwal, RK Wiggert, B Kohn, LD Jamieson, GA Caspi, RR AF Wang, P Sun, SH Silver, PB Chan, CC Agarwal, RK Wiggert, B Kohn, LD Jamieson, GA Caspi, RR TI Methimazole protects from experimental autoimmune uveitis (EAU) by inhibiting antigen presenting cell function and reducing antigen priming SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE autoimmune disease; T lymphocytes; immunoregulation ID SYSTEMIC LUPUS-ERYTHEMATOSUS; GENE-EXPRESSION; DEFICIENT MICE; IFN-GAMMA; INTERFERON; INDUCTION; UVEORETINITIS; THYROCYTES; IL-12; RAT AB Methimazole (methyl-mercapto-imidazole, MMI), a compound used clinically in therapy of Graves' thyroiditis, was found to inhibit development of several autoimmune diseases in animal models. It was suggested on the basis of in vitro data that inhibition is through down-regulation of interferon-gamma (IFN-gamma)-induced expression of major histocompatibility complex class I and class 11 molecules. Here, we investigate the effect of MMI on experimental autoimmune uveoretinitis (EAU) and study its mechanism(s). Treatment of EAU with MMI administered in drinking water inhibited induction of the disease and associated antigen (Ag)specific proliferation and cytokine production by draining lymph node cells (LNCs). The treatment was protective only if administered during the first but not during the second week after immunization,. suggesting an effect on the induction phase of EAU. It is interesting that MMI inhibited disease in IFN-gamma knockout mice, indicating that the in vivo protective effect is IFN-gamma-independent. Flow cytometric analysis of draining LNCs extracted 5 days after immunization showed that MMI partly to completely reversed the increase in Mac-1(+)/class I+/class II+ cells induced by immunization and reduced the proportion of B7-1 and CD40-positive cells, suggesting a deficit in the Ag-presenting cell (APC) population. APC from untreated mice largely restored antigen-specific proliferation of MMI-treated LNCs. We suggest that MMI inhibits EAU at least in part by preventing the recruitment and/or maturation of APC, resulting in reduced generation of Ag-specific T cells. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Ohio Univ, Sch Med, Dept Biomed Sci, Athens, OH 45701 USA. Epigen Consulting Inc, Arlington, MA USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N222,10 Ctr Dr, Bethesda, MD 20892 USA. OI Caspi, Rachel/0000-0002-7140-7671 NR 23 TC 11 Z9 11 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2003 VL 73 IS 1 BP 57 EP 64 DI 10.1189/jlb.0102047 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 636MY UT WOS:000180460900005 PM 12525562 ER PT J AU Rosenberger, TA Villacreses, NE Contreras, MA Bonventre, JV Rapoport, SI AF Rosenberger, TA Villacreses, NE Contreras, MA Bonventre, JV Rapoport, SI TI Brain lipid metabolism in the cPLA(2) knockout mouse SO JOURNAL OF LIPID RESEARCH LA English DT Article DE arachidonate; docosahexaenoate; phospholipase A(2); phospholipid; turnover; kinetics ID CYTOSOLIC PHOSPHOLIPASE A(2); PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYUNSATURATED FATTY-ACIDS; CHRONIC LITHIUM TREATMENT; ACYL-COA SYNTHETASE; ARACHIDONIC-ACID; RAT-BRAIN; INTRACELLULAR CALCIUM; SIGNAL-TRANSDUCTION; TREATMENT DECREASES AB We examined brain phospholipid metabolism in mice in which the cytosolic phospholipase A(2) (cPLA(2) Type IV, 85 kDa) was knocked out (cPLA(2)(-/-) mice). Compared with controls, these mice demonstrated altered brain concentrations of several phospholipids, reduced esterified linoleate, arachidonate, and docosahexaenoate in choline glycerophospholipid, and reduced esterified arachidonate in phosphatidylinositol. Unanesthetized cPLA(2)(-/-) mice had reduced rates of incorporation of unlabeled arachidonate from plasma and from the brain arachidonoyl-CoA pool into ethanolamine glycerophospholipid and choline glycerophospholipid, but elevated rates into phosphatidylinositol. These differences corresponded to altered turnover and metabolic loss of esterified brain arachidonate. These results suggests that cPLA(2) is necessary to maintain normal brain concentrations of phospholipids and of their esterified polyunsaturated fatty acids. M Reduced esterified arachidonate and docosahexaenoate may account for the resistance of the cPLA(2)(-/-) mouse to middle cerebral artery occlusion, and should influence membrane fluidity, neuroinflammation, signal transduction, and other brain processes. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Rosenberger, TA (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NR 75 TC 43 Z9 45 U1 0 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2003 VL 44 IS 1 BP 109 EP 117 DI 10.1194/jlr.M200298-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636VT UT WOS:000180478500013 PM 12518029 ER PT J AU Matsuda, S Matsuda, K Ito, Y AF Matsuda, S Matsuda, K Ito, Y TI Separation of phospholipids and glycolipids using analytical toroidal-coil counter-current chromatography. II. Comparison of the hydrophobicity between Mycoplasma fermentans and human-brain lipids SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE counter-current chromatography; phospholipid; glycolipids; lipid microdomain; Mycoplasma fermentans ID ABSOLUTE-CONFIGURATION; RHEUMATOID ARTHRITIS; CENTRIFUGE; SPEED AB Previously, we reported the successful separation of human-brain lipids by toroidal-coil countercurrent chromatography (TC-CCC) avoiding emulsification and optimizing the solvent systems. In this study, the TC-CCC technique was applied for the analysis of phosphocholine-containing glycoglycerolipids (GGPL-I and GGPL-III) of Mycoplasma fermentans, which is thought to be one of the causative microorganisms of rheumatoid arthritis (RA). Neutral lipids of M. fermentans were separated and their elution profile compared with that of human-brain lipids using a hexane: ethyl acetate: ethanol: 0.1% TFA (5:5:5:4, v/v/v/v) solvent system. In this solvent system, the hydrophobicities of GGPL-III and GGPL-I were similar to those of lysophosphatidylcholine and sphingomyelin (SPM II), respectively. Glycoglycerolipid III was isolated, and further separated into at least two molecular species, using an optimized solvent system composed of hexane :ethyl acetate: ethanol: 0.1% TFA (3 :5: 3 :4, v/v/v/v). The TC-CCC technique is a powerful tool for the separation of lipids of microorganisms, and more importantly, it may become a useful tool for the analysis of a host-pathogen interaction or, in other words, a lipid-protein interaction at lipid microdomains. C1 Natl Canc Ctr, Res Inst, Div Pharmacol, Chuo Ku, Tokyo 1040045, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Horikiri Cent Hosp, Dept Dermatol, Katsushika Ku, Tokyo, Japan. RP Matsuda, K (reprint author), Natl Canc Ctr, Res Inst, Div Pharmacol, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan. EM kmatsuda@gan2.res.ncc.go.jp NR 29 TC 6 Z9 6 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 7 BP 1135 EP 1147 DI 10.1081/JLC-120020099 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 672EF UT WOS:000182507600011 ER PT J AU Han, X Zhang, TY Ito, Y AF Han, X Zhang, TY Ito, Y TI Separation of high purity przewaquinone A by high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE countercurrent chromatography; Salvia miltiorrhiza; przewaquinone A AB High-speed countercurrent chromatography (HSCCC) was used to purify przewaquinone A from the extract of Salvia miltiorrhiza Bunge using a two-phase solvent system composed of carbon tetrachloride-methanol-water-n-hexane, at an optimum volume ratio of 3 : 3 : 2 : 1. The method yielded 15.3 mg of 98% przewaquinone A from 100 mg of a crude sample containing przewaquinone A, at 16.0% in a single run. The recovery of przewaquinone A is as high as 93.7%. Identification was performed by IR, UV, H-1 NMR, C-13 NMR, and FAB-MS. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 8 BP 1267 EP 1274 DI 10.1081/JLC-1200201109 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 671LD UT WOS:000182465500007 ER PT J AU Ito, Y Yang, FQ Fitze, PE Sullivan, JV AF Ito, Y Yang, FQ Fitze, PE Sullivan, JV TI Spiral disk assembly for HSCCC: Column design and basic studies on chromatographic resolution and stationary phase retention SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 2nd International Symposium on Countercurrent Chromatography CY APR 15-20, 2002 CL BEIJING, PEOPLES R CHINA DE spiral disk assembly; countercurrent chromatography; aqueous two phase system; peptide separation; protein separation ID SPEED COUNTERCURRENT CHROMATOGRAPHY AB A set of four separation disks equipped with spiral channel(s) was designed for our type-J high speed countercurrent chromatography (J-HSCCC) centrifuge to improve retention of the stationary phase of polar solvent systems. Four different spiral disks were tested: two had a single spiral channel with different depths and the other two had four spiral channels connected in series to provide a greater spiral pitch. Performance of each disk was tested in terms of chromatographic resolution and/or stationary phase retention using three different two-phase solvent systems, including 1-butanol/acetic acid/water (4:1:5, v/v/v) for dipeptide separation; 12.5% (w/w) polyethylene glycol (PEG) 1000-12.5% (w/w) dibasic potassium phosphate for protein separation; and 4% (w/w) PEG8000-5% (w/w) dextran T500 in 10 mM dibasic sodium phosphate for determination of stationary phase retention. The results show that the spiral column retains a satisfactory amount of stationary phase for all solvent systems, even at a relatively high mobile phase flow rate where the spiral pitch plays a significant role. Separation of dipeptides with the butanol solvent system was possible using 10 mL/min flow rate of the mobile phase and 4-spiral-disks with their greater spiral pitch. In protein separations with the PEG phosphate system, the single-spiral disks yielded the best separation using the upper phase in tail-to-head elution mode at I mL/min, while the 4-spiral disks show higher retention of the stationary phase. The retention of the PEG-dextran system is improved in the 4-spiral disks, which exceed 60% at a How rate of 0.5 mL/min. Various parameters, which affect the performance of the spiral disk separation column are discussed. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. NR 7 TC 39 Z9 42 U1 4 U2 17 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 9-10 BP 1355 EP 1372 DI 10.1081/JLC-120021255 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 698AU UT WOS:000183976100003 ER PT J AU Cao, XL Tian, Y Zhang, TY Liu, QH Jia, LJ Ito, Y AF Cao, XL Tian, Y Zhang, TY Liu, QH Jia, LJ Ito, Y TI Separation of dammarane-saponins from notoginseng, root of Panax notoginseng (Burk.) F.H. Chen, by HSCCC coupled with evaporative light scattering detector SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 2nd International Symposium on Countercurrent Chromatography CY APR 15-20, 2002 CL BEIJING, PEOPLES R CHINA DE CCC; evaporative light scattering detector; saponins; ginsenosides ID TRITERPENE OLIGOGLYCOSIDES; BIOACTIVE SAPONINS; DRIED ROOT; GLYCOSIDES AB High-speed countercurrent chromatography (HSCCC) coupled with evaporative light scattering detection, was applied to the separation of saponins from notoginseng, the main root of Panax. notoginseng (Burk.) F H. Chen. Five individual dammarane saponins have been isolated with the solvent systems composed of CHCl3/MeOH/2-BuOH/H2O (5:6:1:4, v/v/v/v) and EtOAc/1-BuOH/H2O (1:1:2, v/v/v), successively. They were identified as ginsenoside-Rg(1), ginsenoside-Rd, notoginsenoside-R-1, ginsenoside-Re, and ginsenoside-Rb-1, by FAB-MS and C-13 NMR, together with HPLC and TLC analysis. C1 Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, TY (reprint author), Beijing Inst New Technol Applicat, Xizhimen S St 16, Beijing 100035, Peoples R China. NR 10 TC 38 Z9 42 U1 3 U2 15 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 9-10 BP 1579 EP 1591 DI 10.1081/JLC-120021268 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 698AU UT WOS:000183976100016 ER PT J AU Shibusawa, Y Yanagida, A Shindo, H Ito, Y AF Shibusawa, Y Yanagida, A Shindo, H Ito, Y TI Separation of apple catechin oligomers by CCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 2nd International Symposium on Countercurrent Chromatography CY APR 15-20, 2002 CL BEIJING, PEOPLES R CHINA DE countercurrent chromatography; catechin oligomers; tannin; three-phase-system; MALDI-TOF-MS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COUNTER-CURRENT CHROMATOGRAPHY; CELLS IN-VITRO; CONDENSED TANNINS; GRAPE SEEDS; PARTITION CHROMATOGRAPHY; PROMOTE PROLIFERATION; MASS-SPECTROMETRY; SOLID SUPPORT; PROCYANIDINS AB Catechin oligomers with. different degrees of polymerization were separated from apple condensed tannins (ACTs) by countercurrent chromatography using a type-J multilayer coil planet centrifuge. Partition coefficient values for oligomers up to pentamers of catechin and/or epicatechin were determined on hydrophilic two- or three-phase solvent systems. The best separation was achieved using a three-phase solvent system composed of hexane/methyl acetate/acetonitrile/water at a volume ratio of 1 / 1 / 1 / 1, which formed three layers. After the elution of monomers, dimers, trimers, and a part of tetramers using the middle phase, methyl acetate was used as a mobile phase to facilitate elution of the oligomers from tetramers to decamers. These oligomers eluted from the column according to their degree of polymerization. The higher polymerized oligomers over 11-mers were collected from the column with the elution by the lower phase. The masses of the fractionated oligomers were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis using 2',4',6'-trihydroxy acetophenone monohydrate as a matrix. C1 Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, Tokyo 1920392, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, 1432-1 Horinouchi, Tokyo 1920392, Japan. NR 37 TC 22 Z9 22 U1 1 U2 9 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 9-10 BP 1609 EP 1621 DI 10.1081/JLC-120021270 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 698AU UT WOS:000183976100018 ER PT J AU Wei, Y Zhang, TY Xu, GQ Ito, Y AF Wei, Y Zhang, TY Xu, GQ Ito, Y TI Application of CCC for the separation of lutein from a crude extract of marigold flower petals SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 2nd International Symposium on Countercurrent Chromatography CY APR 15-20, 2002 CL BEIJING, PEOPLES R CHINA DE lutein; countercurrent chromatography; carotenoids; marigold flower petal ID COUNTER-CURRENT CHROMATOGRAPHY; BETA-CAROTENE; CANCER; ELUCIDATION; VALIDATION; PLASMA; REDUCE AB Analytical high-speed countercurrent chromatography (HSCCC) was used for the systematic selection and optimization of the two-phase solvent system to separate lutein from the crude extract of the marigold flower petal. Lutein was obtained by preparative HSCCC with a two-phase solvent system composed of n-heptane-chloroform-acetonitrile (10 : 3: 7, v/v/v). HPLC analyses of the lutein revealed that it was over 98.5% purity. The final identification was performed by UV-VIS absorption, H-1-NMR, and C-13-NMR Spectra. C1 Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wei, Y (reprint author), Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China. NR 16 TC 14 Z9 17 U1 4 U2 7 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 9-10 BP 1659 EP 1669 DI 10.1081/JLC-120021274 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 698AU UT WOS:000183976100022 ER PT J AU Du, QZ Ito, Y AF Du, QZ Ito, Y TI Slow rotary countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE slow rotary countercurrent chromatography; stationary phase retention; rotary speed; solvent system; convoluted Teflon tubing; tea extract; epigallocatechin gallate ID ROTATING COIL; SEPARATION AB A number of important parameters affecting the countercurrent chromatography (CCC) technology, including variation of retention of stationary phase, and mixing efficiency with rotational speeds, optimum rotational speed for retention of stationary phase of different,solvent systems, improvement of retention of stationary phase in the column by changing the inner structure of column tubing, and optimum of the column size for a better retention of stationary phases were studied. The results showed that the convoluted tube yielded higher retention of stationary phase than the standard tube, that most solvent systems produced a significant retention of stationary phase at an optimum rotational speed, and that a suitable size column is helpful for retention of stationary phase. Based on the basic studies, an apparatus equipped with a 10 L column of 8.5 mm I.D. convoluted tube was made, and successfully used, to purify 150 g of crude tea extract yielding 40 g of epigallocatechin galllate of over 92.7% purity at a recovery rate of 82.6%. The result suggests that it is possible to further scale up this slow rotary countercurrent chromatograph for industrial use. C1 Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Du, QZ (reprint author), Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. NR 12 TC 7 Z9 7 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 11 BP 1827 EP 1838 DI 10.1081/JLC-120021288 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 698NL UT WOS:000184005600012 ER PT J AU Chao, ZM Shibusawa, Y Shindo, H Ito, Y AF Chao, ZM Shibusawa, Y Shindo, H Ito, Y TI Countercurrent chromatographic purification of polysaccharides from Achyranthes bidentata with an aqueous two-phase system using a cross-axis coil planet centrifuge SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE countercurrent chromatography; cross-axis coil planet centrifuge; polysaccharides; partition coefficient ID PROTEINS; PHASE AB Polysaccharides were purified from a high molecular weight complex of Achyranthes bidentata Bl. (Fam. Amaranthaceae) root by high speed countercurrent chromatography (HSCCC) using a cross-axis coil planet centrifuge (X-axis CPC). The purification was performed with an aqueous polymer two-phase system composed of 12.5% (w/w) polyethylene glycol (PEG) 1000, 8% (w/w) potassium dihydrogen phosphate, and 8% (w/w) dipotassium hydrogen phosphate buffer at pH 6.8. The preparative separation of the crude sample (2 g) was successfully performed, yielding 1.1 g of polysaccharides at high purity. C1 China Acad Tradit Chinese Med, Inst Chinese Mat Med, Beijing 100700, Peoples R China. Tokyo Univ Pharm & Life Sci, Dept Analyt Chem, Sch Pharm, Tokyo, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Chao, ZM (reprint author), China Acad Tradit Chinese Med, Inst Chinese Mat Med, 18 Beixincheng, Beijing 100700, Peoples R China. NR 7 TC 9 Z9 12 U1 2 U2 21 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 12 BP 1895 EP 1903 DI 10.1081/JLC-120021758 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 702BY UT WOS:000184206500004 ER PT J AU Du, QZ Winterhalter, P Ito, Y AF Du, QZ Winterhalter, P Ito, Y TI Large convoluted tubing for scale-up of slow rotary countercurrent chromatograph SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE countercurrent chromatography; slow rotary countercurrent chromatography; scale up AB The chromatographic performance of 1.5 cm I.D. convoluted teflon tubing was studied at low rotary speeds ranging from 34 to 105 rpm. Results were as follows: (i) many solvent systems showed excellent retention of the stationary phase even at a high flow rate of the mobile phase; (ii) a good mixing of the two phases gave efficient solute partitioning resulting in high peak resolution; (iii) increasing the sample size caused only minor peak broadening; and (iv) increase in peak width and resolution using longer columns is predictable. Our data show that it is feasible to scale up a slow rotary countercurrent chromatograph with 1.5 cm I.D. convoluted tubing for industrial use. C1 Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. Tech Univ Carolo Wilhelmina Braunschweig, Inst Food Chem, D-3300 Braunschweig, Germany. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Du, QZ (reprint author), Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. NR 4 TC 7 Z9 8 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 12 BP 1991 EP 2002 DI 10.1081/JLC-120021766 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 702BY UT WOS:000184206500012 ER PT J AU Simmons, TL McCloud, TG AF Simmons, TL McCloud, TG TI Analysis of stibonic acids by ion exchange chromatography with ESI-MS/photodiode array detection SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE stibonic acids; ion exchange chromatography; ESI-MS; photodiode array detection. ID ANTIMONY AB A method utilizing the counter anion exchange properties of aqueous ammonium acetate at pH 9, increasing in concentration linearly from 0 to 0.1 M NH4OAc, using a Hamilton PRP-X100 anion exchange column, is presented for the resolution of aromatic stibonic acids and their detection by UV and ESI mass spectrometry. Additional phase-bonded silica or polymer backed C-8 and C-18 column types, eluted with various counter ion solutions (KClO4, NH4COOH, NaOH, NaH2PO4) were evaluated for suitability for stibonic acid analysis. C1 NCI, SAIC Frederick Inc, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP McCloud, TG (reprint author), NCI, SAIC Frederick Inc, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 10 TC 2 Z9 3 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 13 BP 2041 EP 2051 DI 10.1081/JLC-120022392 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 705ZH UT WOS:000184426800002 ER PT J AU Issaq, HJ Fox, SD Mahadevan, M Conrads, TP Veenstra, TD AF Issaq, HJ Fox, SD Mahadevan, M Conrads, TP Veenstra, TD TI Effect of experimental parameters on the HPLC separation of peptides and proteins SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE proteomics; proteins; peptides; mu HPLC; ESI-MS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; REVERSED-PHASE CHROMATOGRAPHY; IONIZATION MASS-SPECTROMETRY; CAPILLARY COLUMNS; INNER DIAMETERS; TEMPERATURE; MOLECULES; SAMPLES; MICROCOLUMNS AB This manuscript examines the effects of different experimental parameters on resolution, peak symmetry, peak width, and selectivity (peak elution order) of peptides by micro high performance liquid chromatography. The experimental parameters are: mobile phase composition, flow rate, organic modifiers, ion-pairing agents, column temperature, the effect of packing material properties: particle size, particle porosity and reversed-phase (RP) alkyl chain length, and column dimensions. When a mass spectrometer (MS) is used as the detector in micro-HPLC, certain experimental parameters such as mobile phase flow rate and buffer composition have to be adjusted in order to meet the requirements of the MS procedure employed. When electrospray ionization (ESI) is the selected MS mode of operation the mobile phase flow rate should be in nL min(-1) and a volatile buffer should be used to achieve maximum sensitivity. Also, it was found that the elution order (selectivity) of peptides in RP-HPLC is affected by type and concentration of ion-pairing agent, organic modifier, column temperature, pH of the buffer, and the alkyl chain length of the derivatizing agent in RP This manuscript includes work that has been done in Our laboratory and is supplemented by data published by other researchers. C1 NCI Frederick, Analyt Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI Frederick, Analyt Chem Lab, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. NR 29 TC 16 Z9 16 U1 3 U2 8 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 14 BP 2255 EP 2283 DI 10.1081/JLC-120023246 PG 29 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 715QH UT WOS:000184983400004 ER PT J AU Prieto, D Conrads, TP Scudiero, DA Veenstra, TD Issaq, HJ AF Prieto, D Conrads, TP Scudiero, DA Veenstra, TD Issaq, HJ TI Profiling of secreted proteins from human ovarian cancer cell lines by surface-enhanced laser desorption ionization time-of-flight mass spectrometry SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE biomarker detection; protein profile; cancer ID SELDI-TOF MS; PROTEOMICS; SERUM AB Surface-enhanced laser desorption ionization (SELDI) time-of-flight mass spectrometry (TOF MS) was used to profile six human ovarian cancer cell lines. Non-confluent cell cultures were exchanged into serum free medium and allowed to grow for either 24 or 48 hours, at which time the medium was collected and analyzed using a Ciphergen SELDI-TOF MS and a QSTAR Pulsar QqTOF mass spectrometer fitted with a SELDI source. The spectra showed the presence of several low molecular weight species, as well as differences and similarities in the proteins detected in the media of the six ovarian tumor cell lines. The same species were detected at 24 and 48 hours and reproducible changes in their relative abundances were observed. C1 NCI Frederick, Analyt Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI Frederick, In Vitro Cell Line Screening Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI Frederick, Analyt Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 11 TC 4 Z9 4 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 14 BP 2315 EP 2328 DI 10.1081/JLC-120023249 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 715QH UT WOS:000184983400007 ER PT J AU Du, QZ Xia, M Ito, Y AF Du, QZ Xia, M Ito, Y TI Preparation of mevinolinic acid from Monascus purpureus using high-speed countercurrent chromatography (HSCCC) SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Monascus purpureus; mevinolinic acid; preparation; high-speed countercurrent chromatography ID RED-YEAST-RICE; CHOLESTEROL; MEDICINE; FOOD AB High-speed countercurrent chromatography (HSCCC) was applied for the separation of a crude Monascus purpureus extract. The separation was carried out using a two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water (l/l/l/l, v/v) at a flow rate of 1.0 mL/min. From 250 mg of the alkaline treated extract the method yielded 40 mg of mevinolinic acid with a purity of 99% in each separation. The product was confirmed as mevinolinic acid by electrospray ionization multiple mass spectrometry (ESI-MS) and NMR analysis. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3334,50 S Dr MSC 8014, Bethesda, MD 20892 USA. NR 11 TC 6 Z9 8 U1 2 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 18 BP 3085 EP 3092 DI 10.1081/JLC-120025425 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 740HA UT WOS:000186395900009 ER PT J AU Yu, LR Issaq, HJ Conrads, TP Uo, T Blonder, J Janini, GM Morrison, RS Veenstra, TD AF Yu, LR Issaq, HJ Conrads, TP Uo, T Blonder, J Janini, GM Morrison, RS Veenstra, TD TI Evaluation of liquid chromatography-mass spectrometry for routine proteome analyses SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE proteomites; liquid chromatography; mass spectrometry; tandem MS; peptide ID SEPARATION; DISCOVERY AB Many different separation strategies have been developed for conducting proteomic studies, but microcapillary reversed-phase liquid chromatography ( muLC) coupled online to mass spectrometry (MS) has played an undeniably central role. We have conducted a study to evaluate two different common column configurations, along with two common stationary phase materials, for their ability to identify peptides from a complex proteome digest. A 10 cm long x 75 mum inner diameter (id) capillary column with an integrated electrospray tip, and a 30 cm long x 75 mum id capillary column in which the electrospray tip is separated from the separation capillary via a stainless steel union, both packed in-house with reversed phase C-18, 5 mum, 300 Angstrom pore size particles, were evaluated for their ability to effectively resolve a complex mixture of tryptic peptides from a mouse cortical neuron proteome sample for online tandem MS (MS/MS) analysis. The results demonstrate that the continuous 10 cm long x 75 mum id capillary column with the integrated electrospray tip, enables the identification of a comparable number of peptides in a single pLC-MS/MS analysis of a proteome tryptic digestate. We further evaluated the relationship between the numbers of peptides identified vs. the amount of sample loaded onto a 10 cm long x 50 mum id column packed with 3 mum, 100 Angstrom, C-18 reversed phase particles. The results show that more than 100 peptides can be identified from as little as 5 ng of tryptic peptides loaded, and that the number of identified peptides did not significantly increase beyond the loading of 50 ng. C1 NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. RP Veenstra, TD (reprint author), NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, POB B,1050 Boyles St, Frederick, MD 21702 USA. NR 14 TC 3 Z9 3 U1 0 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 20 BP 3331 EP 3342 DI 10.1081/JLC-120025593 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 757XY UT WOS:000187602000001 ER PT J AU Shinomiya, K Kabasawa, Y Nakazawa, H Ito, Y AF Shinomiya, K Kabasawa, Y Nakazawa, H Ito, Y TI Countercurrent chromatographic separation of soybean isoflavones by two different types of coil planet centrifuges with various two-phase solvent systems SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE countercurrent chromatography; isoflavones; coil plant centrifuge; two-phase solvent system ID PURIFICATION AB The countercurrent chromatographic separation of isoflavones from a crude soybean extract was performed with various two-phase solvent systems, using two different types of the coil planet centrifuge (CPC) of the cross-axis CPC and the type-J multilayer CPC. The overall results indicated that the type-J multilayer CPC separates daidzin and genistin with an ethyl acetate/ ethanol/water (4: 2: 7) system at the purity of over 97 and near 100%, respectively, while the cross-axis CPC resolves these compounds in a much longer elution time with an ethyl acetate/1-butanol/water (2: 1 :3) system. The type-J multilayer CPC further resolves daidzein and genistein with an n-hexane/ethyl acetate/1-butanol/methanol/water (5:5:0:5:5) system, and also, simultaneously, all four isoflavones under a linear gradient elution, using the solvent system composed of n-hexane/ethyl acetate/ 1 -butanol/methanol/acetic acid/water by shifting the volume ratio from 1 : 2: 1 :1 : 1 :5 to I : 2: 1 : 3 : 0.5 : 5. The present methods may be useful for the separation of isoflavones from other plant extracts. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. Hoshi Univ, Fac Pharmaceut Sci, Shinagawa Ku, Tokyo 142, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 12 TC 9 Z9 9 U1 0 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2003 VL 26 IS 20 BP 3497 EP 3509 DI 10.1081/JLC-120025604 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 757XY UT WOS:000187602000012 ER PT J AU Schwieters, CD Kuszewski, JJ Tjandra, N Clore, GM AF Schwieters, CD Kuszewski, JJ Tjandra, N Clore, GM TI The Xplor-NIH NMR molecular structure determination package SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; INTERPROTON DISTANCE RESTRAINTS; PROTEIN-STRUCTURE DETERMINATION; COMPLETE CROSS-VALIDATION; STRUCTURE REFINEMENT; CHEMICAL-SHIFTS; 3-DIMENSIONAL STRUCTURE; BACKBONE CONFORMATION; DIPOLAR COUPLINGS; MEAN-FORCE AB We announce the availability of the Xplor-NIH software package for NMR biomolecular structure determination. This package consists of the pre-existing XPLOR program, along with many NMR-specific extensions developed at the NIH. In addition to many features which have been developed over the last 20 years, the Xplor-NIH package contains an interface with a new programmatic framework written in C++. This interface currently supports the general purpose scripting languages Python and TCL, enabling rapid development of new tools, such as new potential energy terms and new optimization methods. Support for these scripting languages also facilitates interaction with existing external programs for structure analysis, structure manipulation, visualization, and spectral analysis. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Schwieters, CD (reprint author), NIH, Div Computat Biosci, Ctr Informat Technol, Bldg 12A, Bethesda, MD 20892 USA. EM Charles.Schwicters@nih.gov; mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 59 TC 1232 Z9 1246 U1 6 U2 87 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2003 VL 160 IS 1 BP 65 EP 73 AR PII S1090-7807(02)00014-9 DI 10.1016/S1090-7807(02)00014-9 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 656YK UT WOS:000181638500010 PM 12565051 ER PT J AU Yordanov, AT Kobayashi, H English, SJ Reijnders, K Milenic, D Krishna, MC Mitchell, JB Brechbiel, MW AF Yordanov, AT Kobayashi, H English, SJ Reijnders, K Milenic, D Krishna, MC Mitchell, JB Brechbiel, MW TI Gadolinium-labeled dendrimers as biometric nanoprobes to detect vascular permeability SO JOURNAL OF MATERIALS CHEMISTRY LA English DT Article ID MR CONTRAST AGENTS; PHARMACOKINETIC PROPERTIES; STARBURST(TM) DENDRIMERS; HIGH-GENERATION; DRUG-DELIVERY; ANTIBODY; RADIOIMMUNOTHERAPY; ANGIOGRAPHY; CARCINOMA; CHEMISTRY AB PAMAM dendrimer-based biometric nanoprobes G4-1B4M-Gd, G6-1B4M-Gd and G8-1B4M-Gd were used to detect vascular permeability in SCCVII mice tumors. Based on the whole body clearance curve, G8-1B4M-Gd emerged as the ideal candidate for vascular permeability imaging studies due to its stable signal enhancement in the tumor over time. A 2D MR image of a SCCVII tumor showed vessel enhancement without obvious diffuse enhancement. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Yordanov, AT (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA. NR 40 TC 34 Z9 34 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0959-9428 J9 J MATER CHEM JI J. Mater. Chem. PY 2003 VL 13 IS 7 BP 1523 EP 1525 DI 10.1039/b304147f PG 3 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 692LA UT WOS:000183661500008 ER PT J AU Ma, SZ Liao, FH Li, SX Xu, MY Li, JR Zhang, SH Chen, SM Huang, RL Gao, S AF Ma, SZ Liao, FH Li, SX Xu, MY Li, JR Zhang, SH Chen, SM Huang, RL Gao, S TI Effect of microstructure, grain size, and rare earth doping on the electrorheological performance of nanosized particle materials SO JOURNAL OF MATERIALS CHEMISTRY LA English DT Article ID COMPLEX STRONTIUM-TITANATE; DOPED TIO2; DISPERSED PARTICLES; RAMAN-SPECTRA; ER FLUIDS; SUSPENSIONS; DEPENDENCE; MECHANISM; ZRO2 AB Nanosized particle materials with different structures and grain sizes were prepared by doping TiO2 or ZrO2 with rare earth (RE) elements, and by changing the method of treatment. Their microstructures were confirmed by X-ray diffraction (XRD) analyses and measurements of the surface areas, pore volumes, and pore sizes of the particles. The electrorheological (ER) performance and dielectric properties of these materials, and the relationship between ER activity, microstructure, and grain size of these particle materials were investigated. The results have shown that RE doping can either increase or decrease the ER activity of a material, which is related to the pore volume in the grain. Body-centered tetragonal TiO2 and tetragonal ZrO2 possess higher ER activity than tetragonal TiO2 and monoclinic ZrO2, respectively. The effect of grain size on ER performance should not be neglected for different materials in a system with identical crystal structure and composition, and the co-action of both larger grain size and larger pore volume can play a very important role in nanosized particle materials. Optimal matching between appropriate RE-doping, microstructure and particle size, which can be achieved by fine-tuning the production process of a material, may provide a basis for producing an ER material with high activity. C1 Peking Univ, Coll Chem & Mol Engn, State Key Lab Rare Earth Mat Chem & Applicat, Beijing 100871, Peoples R China. Baoding Teachers Coll, Dept Chem, Baoding 071051, Peoples R China. Beijing Inst Technol, Sch Vehicle & Transmiss Engn, Beijing 100081, Peoples R China. Fuzhou Univ, Dept Mech Engn, Fuzhou 350002, Peoples R China. NCI, Frederick, MD 21702 USA. RP Li, JR (reprint author), Peking Univ, Coll Chem & Mol Engn, State Key Lab Rare Earth Mat Chem & Applicat, Beijing 100871, Peoples R China. NR 35 TC 26 Z9 27 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0959-9428 J9 J MATER CHEM JI J. Mater. Chem. PY 2003 VL 13 IS 12 BP 3096 EP 3102 DI 10.1039/b306996f PG 7 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 749FB UT WOS:000186907500052 ER PT J AU Whitaker, SY Tran, HT Portier, CJ AF Whitaker, SY Tran, HT Portier, CJ TI Development of a biologically-based controlled growth and differentiation model for developmental toxicology SO JOURNAL OF MATHEMATICAL BIOLOGY LA English DT Article DE teratology; multistate process; cellular kinetics; numerical simulation ID STOCHASTIC 2-STAGE MODEL; CANCER RISK ASSESSMENT; MULTISTAGE MODEL; CARCINOGENESIS; NUMBER; CLONES; TUMOR; SIZE; FOCI AB A mathematical model is developed with a highly controlled birth and death process for precursor cells. This model is both biologically- and statistically-based. The controlled growth and differentiation (CGD) model limits the number of replications allowed in the development of a tissue or organ and thus, more closely reflects the presence of a true stem cell population. Leroux et al. (1996) presented a biologically-based dose-response model for developmental toxicology that was derived from a partial differential equation for the generating function. This formulation limits further expansion into more realistic models of mammalian development. The same formulae for the probability of a defect (a system of ordinary differential equations) can be derived through the Kolmogorov forward equations due to the nature of this Markov process. This modified approach is easily amenable to the expansion of more complicated models of the developmental process such as the one presented here. Comparisons between the Leroux et al. (1996) model and the controlled growth and differentiation (CGD) model as developed in this paper are also discussed. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Math, Ctr Res Sci Computat, Raleigh, NC 27695 USA. RP Whitaker, SY (reprint author), NIEHS, Lab Computat Biol & Risk Anal, 111 T W Alexander Dr,Bldg 101,MD A3-06, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 18 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0303-6812 J9 J MATH BIOL JI J. Math. Biol. PD JAN PY 2003 VL 46 IS 1 BP 1 EP 16 DI 10.1007/s00285-002-0164-8 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 643RJ UT WOS:000180874000001 PM 12525932 ER PT J AU Bader, JL Theofanos, MF AF Bader, Judith L. Theofanos, Mary Frances TI Searching for Cancer Information on the Internet: Analyzing Natural Language Search Queries SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Cancer; Internet; search engines; natural language processing ID WORLD-WIDE-WEB; BREAST-CANCER; HEALTH INFORMATION; PROSTATE-CANCER; ONCOLOGY; QUALITY; PATIENT; SEEKING; IMPACT; MAIL AB Background: Searching for health information is one of the most-common tasks performed by Internet users. Many users begin searching on popular search engines rather than on prominent health information sites. We know that many visitors to our (National Cancer Institute) Web site, cancer. gov, arrive via links in search engine result. Objective: To learn more about the specific needs of our general-public users, we wanted to understand what lay users really wanted to know about cancer, how they phrased their questions, and how much detail they used. Methods: The National Cancer Institute partnered with AskJeeves, Inc to develop a methodology to capture, sample, and analyze 3 months of cancer-related queries on the Ask.com Web site, a prominent United States consumer search engine, which receives over 35 million queries per week. Using a benchmark set of 500 terms and word roots supplied by the National Cancer Institute, AskJeeves identified a test sample of cancer queries for 1 week in August 2001. From these 500 terms only 37 appeared >= 5 times/day over the trial test week in 17208 queries. Using these 37 terms, 204165 instances of cancer queries were found in the Ask.com query logs for the actual test period of June-August 2001. Of these, 7500 individual user questions were randomly selected for detailed analysis and assigned to appropriate categories. The exact language of sample queries is presented. Results: Considering multiples of the same questions, the sample of 7500 individual user queries represented 76077 queries (37% of the total 3-month pool). Overall 78.37% of sampled Cancer queries asked about 14 specific cancer types. Within each cancer type, queries were sorted into appropriate subcategories including at least the following: General Information, Symptoms, Diagnosis and Testing, Treatment, Statistics, Definition, and Cause/Risk/Link. The most-common specific cancer types mentioned in queries were Digestive/Gastrointestinal/Bowel (15.0%), Breast (11.7%), Skin (11.3%), and Genitourinary (10.5%). Additional subcategories of queries about specific cancer types varied, depending on user input. Queries that were not specific to a cancer type were also tracked and categorized. Conclusions: Natural-language searching affords users the opportunity to fully express their information needs and can aid users naive to the content and vocabulary. The specific queries analyzed for this study reflect news and research studies reported during the study dates and would surely change with different study dates. Analyzing queries from search engines represents one way of knowing what kinds of content to provide to users of a given Web site. Users ask questions using whole sentences and keywords, often misspelling words. Providing the option for natural-language searching does not obviate the need for good information architecture, usability engineering, and user testing in order to optimize user experience. C1 [Bader, Judith L.; Theofanos, Mary Frances] NCI, Off Commun Canc Informat Prod & Serv, Commun Technol Branch, Bethesda, MD 20852 USA. RP Bader, JL (reprint author), NCI, Off Commun Canc Informat Prod & Serv, Commun Technol Branch, 6116 Execut Blvd,Suite 3048A, Bethesda, MD 20852 USA. EM jbader@mail.nih.gov FU Cherie Nichols and Bernard Glassman of the Office of Science Policy; AskJeeves, Inc FX The natural-language-processing project was initiated and funded at NCI by Cherie Nichols and Bernard Glassman of the Office of Science Policy. The project was supported programmatically by Janice Nall, William Trefzger, and Su Hubbard. At AskJeeves, Inc, several staff members provided important technical and programmatic support, including the production of a final report to NCI upon which this paper is based. These individuals are Jeff Hjelt, Rob Thomson, and Kent Schmitt. NR 38 TC 25 Z9 25 U1 2 U2 10 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2003 VL 5 IS 4 AR e31 DI 10.2196/jmir.5.4.e31 PG 15 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA V12UY UT WOS:000207625300006 PM 14713659 ER PT J AU Bader, JL Strickman-Stein, N AF Bader, Judith L. Strickman-Stein, Nancy TI Evaluation of New Multimedia Formats for Cancer Communications SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Lung cancer; Internet; multimedia; patient education; audio AB Background: Providing quality, current cancer information to cancer patients and their families is a key function of the National Cancer Institute (NCI) Web site. This information is now provided in predominantly-text format, but could be provided in formats using multimedia, including animation and sound. Since users have many choices about where to get their information, it is important to provide the information in a format that is helpful and that they prefer. Objective: To pilot and evaluate multimedia strategies for future cancer-information program formats for lay users, the National Cancer Institute created new multimedia versions of existing text programs. We sought to evaluate user performance and preference on these 3 new formats and on the 2 existing text formats. Methods: The National Cancer Institute's "What You Need to Know About Lung Cancer" program was the test vehicle. There were 5 testing sessions, 1 dedicated to each format. Each session lasted about 1 hour, with 9 participants per session and 45 users overall. Users were exposed to the assigned cancer program from beginning to end in 1 of 5 formats: text paperback booklet, paperback booklet formatted in HTML on the Web, spoken audio alone, spoken audio synchronized with a text Web page, and Flash multimedia (animation, spoken audio, and text). Immediately thereafter, the features and design of the 4 alternative formats were demonstrated in detail. A multiple-choice pre-test and post-test quiz on the cancer content was used to assess user learning (performance) before and after experiencing the assigned program. The quiz was administered using an Authorware software interface writing to an Access database. Users were asked to rank from 1 to 5 their preference for the 5 program formats, and provide structured and open-ended comments about usability of the 5 formats. Results: Significant improvement in scores from pre-test to post-test was seen for the total study population. Average scores for users in each of the 5 format groups improved significantly. Increments in improvement, however, were not statistically different between any of the format groups. Significant improvements in quiz scores were seen irrespective of age group or education level. Of the users, 71.1% ranked the Flash program first among the 5 formats, and 84.4% rated Flash as their first or second choice. Audio was the least-preferred format, ranking fifth among 46.7% of users and first among none. Flash was ranked first among users regardless of education level, age group, or format group to which the user was assigned. Conclusions: Under the pilot study conditions, users overwhelmingly preferred the Flash format to the other 4 formats. Learning occurred equally in all formats. Use of multimedia should be considered as communication strategies are developed for updating cancer content and attracting new users. C1 [Bader, Judith L.] NCI, Commun Technol Branch, Off Commun, Canc Informat Prod & Serv, Bethesda, MD 20852 USA. [Strickman-Stein, Nancy] Miami Vet Affairs Med Ctr GRECC, Miami, FL USA. [Strickman-Stein, Nancy] Univ Sch Med, Div Gerontol & Geriatr Med, Miami, FL USA. RP Bader, JL (reprint author), NCI, Commun Technol Branch, Off Commun, Canc Informat Prod & Serv, 6116 Execut Blvd,Suite 3048A, Bethesda, MD 20852 USA. EM jbader@mail.nih.gov NR 26 TC 27 Z9 30 U1 0 U2 2 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2003 VL 5 IS 3 AR e16 DI 10.2196/jmir.5.3.e16 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA V12UX UT WOS:000207625200002 PM 14517107 ER PT J AU Praetorius, HA Spring, KR AF Praetorius, HA Spring, KR TI Removal of the MDCK cell primary cilium abolishes flow sensing SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE chloral hydrate; microtubules; immunefluorescence; calcium ID CALCIUM CHANNELS; CATION CHANNEL; DIFFUSION AB The hypothesis that cell primary cilium is solely responsible for the flow-induced Ca2+ response in MDCK cells was tested by removal of the cilia from mature, responsive cells. Incubation of the cells with 4 mM chloral hydrate for 68 hours resulted in the complete loss of the primary cilia and in disorganization of microtubules, as visualized by immunofluorescence. When intracellular Ca2+ concentration was measured with Fluo-4, the elevation that normally accompanies an increase in fluid flow was abolished after 20 hours exposure to chloral hydrate. At this time, the primary cilia still remained attached to the cells but had become twisted and flexible. Twenty four hours after return of the deciliated cells to normal medium, intracellular microtubule organization appeared normal, but primary cilia had not yet been expressed. The cells failed to increase intracellular Ca2+ in response to fluid flow until after they had been in normal medium for 120 hours, at which time the primary cilia were 3-4 mum long. Chloral hydrate did not impair the Ca2+ mobilization machinery, as the Ca2+ response to mechanical contact and the spread to neighboring cells was unaffected by the drug. We conclude that the primary cilium is the only sensor for the flow-induced Ca2+ response in MDCK cells and estimate that a single mechanically sensitive channel in the cilium could provide the requisite Ca2+ influx. C1 Aarhus Univ, IEKF, Water & Salt Res Ctr, DK-8200 Aarhus N, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Praetorius, HA (reprint author), Aarhus Univ, IEKF, Water & Salt Res Ctr, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. NR 16 TC 197 Z9 206 U1 1 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JAN 1 PY 2003 VL 191 IS 1 BP 69 EP 76 DI 10.1007/s00232-002-1042-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 637YH UT WOS:000180541000007 PM 12532278 ER PT J AU Karpova, TS Baumann, CT He, L Wu, X Grammer, A Lipsky, P Hager, GL McNally, JG AF Karpova, TS Baumann, CT He, L Wu, X Grammer, A Lipsky, P Hager, GL McNally, JG TI Fluorescence resonance energy transfer from cyan to yellow fluorescent protein detected by acceptor photobleaching using confocal microscopy and a single laser SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE acceptor photobleaching; argon laser; CFP; confocal microscopy; FRET; YFP ID NECROSIS-FACTOR RECEPTOR; GPI-ANCHORED PROTEINS; FRET MICROSCOPY; LIVING CELLS; CHOLERA-TOXIN; HUMAN TRAF2; ACTIVATION; ASSOCIATION; RECOGNITION; FAMILY AB One manifestation of fluorescence resonance energy transfer (FRET) is an increase in donor fluorescence after photobleaching the acceptor. Published acceptor-photobleaching methods for FRET have mainly used wide-field microscopy. A laser scanning confocal microscope enables faster and targeted bleaching within the field of view, thereby improving speed and accuracy. Here we demonstrate the approach with CFP and YFP, the most versatile fluorescent markers now available for FRET. CFP/YFP FRET imaging has been accomplished with a single laser (argon) available on virtually all laser-scanning confocal microscopes. Accordingly, we also describe the conditions that we developed for dual imaging of CFP and YFP with the 458 and 514 argon lines. We detect FRET in a CFP/YFP fusion and also between signalling molecules (TNF-Receptor-Associated-Factors or TRAFs) that are known to homo- and heterotrimerize. Importantly, we demonstrate that appropriate controls are essential to avoid false positives in FRET by acceptor photobleaching. We use two types of negative control: (a) an internal negative control (non-bleached areas of the cell) and (b) cells with donor in the absence of the acceptor (CFP only). We find that both types of negative control can yield false FRET. Given this false FRET background, we describe a method for distinguishing true positive signals. In summary, we extensively characterize a simple approach to FRET that should be adaptable to most laser-scanning confocal microscopes, and demonstrate its feasibility for detecting FRET between several CFP/YFP partners. C1 NCI, CCR Core Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NIAMS, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, CCR Core Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, 41 Lib, Bethesda, MD 20892 USA. NR 37 TC 228 Z9 234 U1 2 U2 29 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD JAN PY 2003 VL 209 BP 56 EP 70 DI 10.1046/j.1365-2818.2003.01100.x PN 1 PG 15 WC Microscopy SC Microscopy GA 635UB UT WOS:000180416800008 PM 12535185 ER PT J AU Elias, AF Bono, JL Kupko, JJ Stewart, PE Krum, JG Rosa, PA AF Elias, AF Bono, JL Kupko, JJ Stewart, PE Krum, JG Rosa, PA TI New antibiotic resistance cassettes suitable for genetic studies in Borrelia burgdorferi SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Borrelia burgdorferi; antibiotic resistance; selectable marker; gene inactivation; shuttle vector ID LYME-DISEASE SPIROCHETE; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; CIRCULAR PLASMID; TRANSFORMATION; RECOMBINATION; INACTIVATION; MUTAGENESIS; HOMOLOGY; EXCHANGE AB In this report we describe two distinct approaches to develop new antibiotic resistance cassettes that allow for efficient selection of Borrelia burgdorferi transformants. The first approach utilizes fusions of borrelial flagellar promoters to antibiotic resistance markers from other bacteria. The aacC1 gene, which encodes a gentamicin acetyltransferase, conferred a high level of gentamicin resistance in B. burgdorferi when expressed from these promoters. No cross-resistance occurred between this cassette and the kanamycin resistance cassette, which was previously developed in an analogous fashion. A second and different approach was taken to develop an efficient selectable marker that confers resistance to the antibiotic coumermycin A1. A synthetic gene was designed from the gyrB301 allele of the cournermycin-resistant B. burgdorferi strain B31-NGR by altering the coding sequence at the wobble position. The resulting gene, gyrB(syn), encodes a protein identical to the product of gyrB301, but the genes share only 66% nucleotide identity. The nucleotide sequence of gyrB(syn) is sufficiently divergent from the endogenous B. burgdorferi gyrB gene to prevent recombination between them. The cassettes described in this paper improve our repertoire of genetic tools in B. burgdorferi. These studies also provide insight into parameters governing recombination and gene expression in B. burgdorferi. Copyright (C) 2003 S. Karger AG, Basel. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogensis, NIH, Hamilton, MT 59840 USA. RP Elias, AF (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogensis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 26 TC 86 Z9 89 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2003 VL 6 IS 1 BP 29 EP 40 DI 10.1159/000073406 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 745HQ UT WOS:000186683600005 PM 14593251 ER PT J AU Nikolskaya, AN Mulkidjanian, AY Beech, IB Galperin, MY AF Nikolskaya, AN Mulkidjanian, AY Beech, IB Galperin, MY TI MASE1 and MASE2: Two novel integral membrane sensory domains SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE signal transduction; genome analysis; Escherichia coli; adenylate cyclase; histidine kinase; membrane topology ID SALMONELLA-TYPHIMURIUM; TOPOLOGY PREDICTION; GGDEF DOMAIN; PROTEIN; RECEPTORS; DATABASE; EVOLUTION; CYCLASE; COMMON; OXYGEN AB Escherichia coli proteins YegE and YaiC contain N-terminal integral membrane regions, followed by the putative diguanylate cyclase (GGDEF, DUF1) domains. The membrane domains of these proteins, named MASE1 (membrane-associated sensor) and MASE2, respectively, were found in other bacterial signaling proteins, such as histidine kinases (MASE1) and an adenylate cyclase (MASE2). Although the nature of the signals sensed by MASE1 and MASE2 is still unknown, MASE1-containing receptors appear to play important roles in bacteria, including iron and/or oxygen sensing by hemerythrine-containing proteins in the sulfate-reducing bacterium Desulfovibrio vulgaris. Copyright (C) 2003 S. Karger AG, Basel. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ Osnabruck, Dept Biol & Chem, Div Biophys, D-49069 Osnabruck, Germany. Univ Portsmouth, Sch Pharm & Biomed Sci, Portsmouth, Hants, England. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064 NR 31 TC 37 Z9 38 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2003 VL 5 IS 1 BP 11 EP 16 DI 10.1159/000068720 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 681YU UT WOS:000183063800003 PM 12673057 ER PT J AU Jordan, IK Henze, K Fedorova, ND Koonin, EV Galperin, MY AF Jordan, IK Henze, K Fedorova, ND Koonin, EV Galperin, MY TI Phylogenomic analysis of the Giardia intestinalis transcarboxylase reveals multiple instances of domain fusion and fission in the evolution of biotin-dependent enzymes SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE pyruvate carboxylase; oxaloacetate decarboxylase; acetyl-CoA carboxylase; biotin; domain fusion; phylogenetic tree ID ACETYL-COA CARBOXYLASE; COENZYME-A CARBOXYLASE; PYRUVATE-CARBOXYLASE; AMITOCHONDRIATE PROTIST; ENTAMOEBA-HISTOLYTICA; BIOCHEMICAL-CHARACTERIZATION; PROTEIN SEQUENCES; TREE TOPOLOGIES; LAMBLIA; GENE AB Sequencing of the gene encoding a pyruvate carboxylase-like protein from the amitochondrial eukaryote Giardia intestinalis revealed a 1,338 aa protein composed of acetyl-CoA carboxyltransferase (ACCT), pyruvate carboxyltransferase (PycB), and biotin carboxyl carrier protein (BCCP) domains, linked in a single polypeptide chain. This particular domain combination has been previously seen only in the methylmalonyl-CoA:pyruvate transcarboxylase from Propionibacterium freudenreichii, where each of these domains is encoded by an individual gene and forms a separate subunit. To get an insight into the evolutionary origin and biochemical function of the G. intestinalis enzyme, we compared its domain composition to those of other biotin-dependent enzymes and performed a phylogenetic analysis of each of its domains. The results obtained indicate that: (1) evo-lution of the BCCP domain included several domain fusion events, leading to the ACCT-BCCP and PycB-BCCP domain combinations; (2) fusions of the PycB and BCCP domains in pyruvate carboxylases and oxaloacetate decarboxylases occurred on several independent occasions in different prokaryotic lineages, probably due to selective pressure towards co-expression of these genes, and (3) because newly sequenced biotin-dependent enzymes are often misannotated in sequence databases, their annotation as either carboxylases, decarboxylases, or transcarboxylases has to rely on detailed analysis of their domain composition, operon organization of the corresponding genes, gene content in the particular genome, and phylogenetic analysis. Copyright (C) 2003 S. Karger AG, Basel. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Rockefeller Univ, New York, NY 10021 USA. Univ Dusseldorf, Inst Bot 3, D-4000 Dusseldorf, Germany. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013; Abrams, Natalie/F-4845-2011 OI Galperin, Michael/0000-0002-2265-5572; Abrams, Natalie/0000-0001-9698-2819 FU NIAID NIH HHS [AI11942] NR 73 TC 10 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2003 VL 5 IS 3 BP 172 EP 189 DI 10.1159/000070268 PG 18 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 686LK UT WOS:000183323100006 PM 12766347 ER PT J AU Ponomarev, VA Makarova, KS Aravind, L Koonin, EV AF Ponomarev, VA Makarova, KS Aravind, L Koonin, EV TI Gene duplication with displacement and rearrangement: Origin of the bacterial replication protein PriB from the single-stranded DNA-Binding protein ssb SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE PriB; primosome; Ssb; duplication; operon rearrangement ID ESCHERICHIA-COLI K-12; EVOLUTION; GENOMES; PRIMOSOME; DATABASE; SEQUENCE; DOMAIN AB PriB is a proteobacterial protein that is involved in the pre-primosomal step of DNA replication and, unexpectedly, is encoded with a ribosomal protein operon. Detailed sequence comparisons and analysis of operon organization show that PriB evolved from the single-stranded DNA-binding (Ssb) via gene duplication with subsequent rapid sequence diversification. Duplication of the ssb gene was accompanied by a genome rearrangement which resulted in one of the paralogs retaining the original position, whereas the other was relocated. The functional specialization of the resulting paralogs apparently proceeded in an unexpected fashion: the original Ssb function remained with the relocated paralog, whereas the one within the ribosomal protein operon acquired a new, specialized function in replication. Copyright (C) 2003 S. Karger AG, Basel. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 27 TC 14 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2003 VL 5 IS 4 BP 225 EP 229 DI 10.1159/000071074 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 704LN UT WOS:000184341300004 PM 12867746 ER PT J AU Gozes, I Divinsky, I Pilzer, I Fridkin, M Brenneman, DE Spier, AD AF Gozes, I Divinsky, I Pilzer, I Fridkin, M Brenneman, DE Spier, AD TI From vasoactive intestinal peptide (VIP) through activity-dependent neuroprotective protein (ADNP) to NAP - A view of neuroprotection and cell division SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE peptides; neuroprotection; cell division ID STIMULATES PROLIFERATION; FATTY NEUROPEPTIDE; ALZHEIMERS-DISEASE; NEURONAL CULTURES; DEVELOPING BRAIN; HEAD-INJURY; PC12 CELLS; WATER MAZE; ANALOG; GROWTH AB Accelerated neuronal death brings about cognitive as well as motor and other dysfunctions. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective. However, VIP-based drug design is hampered by the instability of the peptide and its limited bioavailability. Two independent approaches were thus taken to exploit VIP as a lead drug candidate: (1) Potent neuroprotective lipophilic analogs of VIP were synthesized, e.g. [stearyl-norleucine-17] VIP (SNV); and (2) potent neuroprotective peptide derivatives were identified that mimic the activity of VIP-responsive neuroprotective glial proteins. VIP provides neuronal defense by inducing the synthesis and secretion of neuroprotective proteins from astrocytes; activity-dependent neuroprotective protein (ADNP) was discovered as such glial cell mediator of VIP- and SNV-induced neuroprotection. In subsequent studies, an eight-amino-acid peptide, NAP, was identified as the smallest active element of ADNP exhibiting potent neuroprotective activities. This paper summarizes the biological effects of SNV and NAP and further reports advances in NAP studies toward clinical development. An original finding described here shows that NAP, while protecting neurons, demonstrated no apparent effect on cell division in a multiplicity of cell lines, strengthening the notion that NAP is a specific neuroprotective drug candidate. C1 Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-78100 Rehovot, Israel. NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 37 TC 73 Z9 75 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2003 VL 20 IS 3 BP 315 EP 322 DI 10.1385/JMN:20:3:315 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 726BT UT WOS:000185578800016 PM 14501014 ER PT J AU Sellers, JR Wang, F Chantler, PD AF Sellers, JR Wang, F Chantler, PD TI Trifluoperazine inhibits the MgATPase activity and in vitro motility of conventional and unconventional myosins SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; REGULATORY LIGHT-CHAIN; PHOSPHORYLATION-DEPENDENT REGULATION; ATPASE ACTIVITY; ACTIN; PHOSPHODIESTERASE; CONTRACTION; SUPERFAMILY; MECHANISM; BINDING AB Trifluoperazine, a calmodulin antagonist, has recently been shown to inhibit the MgATPase activity of scallop myosin in the absence of light chain dissociation ( Patel et al. ( 2000) J Biol Chem 275: 4880 - 4888). To investigate the generality of this observation and the mechanism by which it occurs, we have examined the ability of trifluoperazine to inhibit the enzymatic properties of other conventional and unconventional myosins. We show that trifluoperazine can inhibit the actin- activated MgATPase activity of rabbit skeletal muscle myosin II heavy meromyosin ( HMM), phosphorylated turkey gizzard smooth muscle myosin II HMM, phosphorylated human nonmuscle myosin IIA HMM and myosin V subfragment- 1 ( S1). In all cases half maximal inhibition occurred at 50 - 75 muM trifluoperazine while light chains ( myosin II) or calmodulin ( myosin V) remained associated with the heavy chains. In vitro motility of all myosins tested was completely inhibited by trifluoperazine. Chymotryptic digestion of baculovirus- expressed myosin V HMM possessing only two calmodulin binding sites yielded a minimal motor fragment with no bound calmodulin. The MgATPase of this fragment was inhibited by trifluoperazine over the same range of concentrations as the S1 fragment of myosin. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Univ London Royal Coll Vet Surg, Unit Mol & Cellular Biol, London NW1 OTU, England. RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 35 TC 3 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PY 2003 VL 24 IS 8 BP 579 EP 585 DI 10.1023/B:JURE.0000009969.04562.58 PG 7 WC Cell Biology SC Cell Biology GA 757AE UT WOS:000187517300011 PM 14870973 ER PT J AU Hayashi, K Nakanishi, Y Bastow, KF Cragg, G Nozaki, H Lee, KH AF Hayashi, K Nakanishi, Y Bastow, KF Cragg, G Nozaki, H Lee, KH TI Antitumor agents. 221. Buceracidins A and B, two new flavanones from Bucida buceras SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB As part of a study on antitumor agents from rainforest plants, two new flavanones, buceracidin A (1), 5,2'-dihydroxy-3-methoxy-6,7-(2",2"-(dimethylehromene)flavanone, and buceracidin B (2), 5,2'-dihydroxy-6,7-(2",2"-dimethylehromene)flavanone, were isolated together with four known prenylated flavanones, minimiflorin (3), 3-hydroxyminimiflorin (4), 3-methoxyminimiflorin (5), and mundulinol (6), from Bucida buceras. The structures of buceracidins A and B were elucidated from detailed 2D NMR analyses. Among the six flavanones, 3, 5, and 6 were marginally cytotoxic in a human tumor cell line panel. C1 Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. Okayama Univ Sci, Dept Biochem, Okayama 7000005, Japan. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA. EM khlee@une.edu FU NCI NIH HHS [CA-17625] NR 8 TC 13 Z9 13 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 2003 VL 66 IS 1 BP 125 EP 127 DI 10.1021/np0203483 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 639HX UT WOS:000180623400027 PM 12542360 ER PT J AU Abbott, KC Bucci, JR Agodoa, LY AF Abbott, KC Bucci, JR Agodoa, LY TI Total hip arthroplasty in chronic dialysis patients in the United States SO JOURNAL OF NEPHROLOGY LA English DT Article DE total hip arthroplasty; revision; repeat; complications; mortality; dialysis; gender; male; female; diabetes; systemic lupus erythematosus; osteoarthritis; avascular necrosis of the hip; African American; body mass index; risk; age; weight; complications; USRDS ID STAGE RENAL-DISEASE; RISK-FACTORS; OSTEOARTHRITIS; MEN; TRANSPLANTATION; FRACTURE; SIZE AB Background. The national incidence of and factors associated with total hip arthroplasty (THA) in chronic dialysis patients has never been reported. Methods: We therefore performed an historical cohort study of 375,857 chronic dialysis patients listed in the 2000 United States Renal Data System between I April 1995 and 31 December 1999 and followed-up until 14 May 2000. Primary outcomes were associations with hospitalizations for a primary discharge code of THA (ICD9 procedure code 81.51x) after initiation of dialysis. Results: Dialysis patients had a cumulative incidence of THA of 35 episodes/10,000 person-years, compared to 5.3/10,000 in the general population. The leading indication for THA was osteoarthritis of the hip and pelvis (58% of cases). However, the strongest risk factor for THA in dialysis patients was end-stage renal disease (ESRD) due to systemic lupus erythematosus; (SLE, adjusted rate ratio (ARR), 6.80, 95% CI 4.62-10.03, in whom avascular necrosis of the hip was the most common indication, 68.4%). The database did not include information on use of corticosteroids. Diabetic recipients were significantly less likely to receive THA, as were males, and African Americans. Mortality after THA was 0.25% at thirty days and 30% at three years, not significantly different from the expected mortality of dialysis, adjusted for comorbidity. Conclusions: The most common indication for THA in dialysis patients is osteoarthritis of the hip, similar to the general population. Patients with SLE are more likely to receive THA which is well tolerated and not associated with increased mortality in this population, perhaps reflecting selection bias due to appropriate screening for this elective procedure. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Dialysis Nephrol Serv, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 27 TC 16 Z9 17 U1 0 U2 7 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1121-8428 J9 J NEPHROL JI J. Nephrol. PD JAN-FEB PY 2003 VL 16 IS 1 BP 34 EP 39 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 652AC UT WOS:000181355700005 PM 12649533 ER PT J AU Abbott, KC Glanton, CW Agodoa, LY AF Abbott, KC Glanton, CW Agodoa, LY TI Body mass index and enrollment on the renal transplant waiting list in the United States SO JOURNAL OF NEPHROLOGY LA English DT Article DE body mass index; obesity; renal transplantation; waiting list; female; Caucasian; African American; diabetes; age ID RISK FACTOR; HEMODIALYSIS-PATIENTS; BACTERIAL SEPTICEMIA; CHRONIC DIALYSIS; VASCULAR ACCESS; MORTALITY; OBESITY; GENDER; IMPACT; HOSPITALIZATIONS AB Background: Previous studies of body mass index (BMI) and enrollment on the renal transplant waiting list have not analyzed a national population of chronic dialysis patients. Methods: 161,265 patients in the United States Renal Data System (USRDS) initiated on end-stage renal disease (ESRD) therapy between 1 April 1995 and 30 June 1997 who had data sufficient to calculate BMI were analyzed in an historical cohort study. Cox Regression analysis was used to model the association of BMI and rates of listing for renal transplantation, censored for death and receipt of renal transplant, and adjusted for demographics, comorbidities in the Medical Evidence Form (2728) and in comparison with patient survival. Results: In univariate analysis, only patients with BMI <21.3 kg/m(2) had a statistically significant lower rate of listing compared to patients with BMI 24.5-28.6 kg/m(2) (6.1 vs. 7.5/100 person years). In Cox Regression analysis, patients with BMI <21.3 kg/m(2) had a 18% lower adjusted rate of listing and a 38% lower rate of survival, and patients with BMI greater than or equal to24.5-28.7 had an 11% higher adjusted rate of listing and no significant difference in adjusted survival compared with patients with BMIgreater than or equal to28.7 kg/m(2). Caucasian females were disproportionately affected by high BMI. Conclusions: Among ESRD patients, lower BMI was independently associated with reduced adjusted rates of listing. High BMI affected rates of listing disproportionately in caucasian females. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), 7 Rudis Way, Gaithersburg, MD 20878 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 25 TC 19 Z9 19 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1121-8428 J9 J NEPHROL JI J. Nephrol. PD JAN-FEB PY 2003 VL 16 IS 1 BP 40 EP 48 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 652AC UT WOS:000181355700006 PM 12649534 ER PT J AU Matsumoto, C Swanson, SJ Agodoa, LY Holtzmuller, KC Abbott, KC AF Matsumoto, C Swanson, SJ Agodoa, LY Holtzmuller, KC Abbott, KC TI Hospitalized gastrointestinal bleeding and procedures after renal transplantation in the United States SO JOURNAL OF NEPHROLOGY LA English DT Article DE gastrointestinal bleeding; hospitalization; renal transplant; African American; rejection; graft loss; USRDS ID HELICOBACTER-PYLORI INFECTION; CYTOMEGALOVIRUS; HEMODIALYSIS; RECIPIENT; DISEASE; FAILURE; HEMORRHAGE AB The risk of hospitalized gastrointestinal bleeding (GIB) in renal transplant recipients has not been studied in a national renal transplant population. Therefore, 42,906 renal transplant recipients in the United States Renal Data System (USRDS) from 1 July 1994 - 30 June 1998 were analyzed in an historical cohort study of hospitalizations with a primary discharge diagnosis of GIB (ICD9 Code 578.9x) using Cox regression analysis. The 1997 National Hospital Discharge Survey was used to obtain rates of GIB for the general population. Renal transplant recipients had a cumulative incidence of hospitalizations for GIB of 334 events/100,000 person-years. In 1997, compared to the general population, renal transplant recipients had an age-adjusted rate ratio for GIB of 10.69 at one year of follow-up. The strongest risk factors for GIB in Cox regression analysis were graft loss (adjusted hazard ratio, 4.28 (2.84-6.47) and African American recipients who experienced allograft rejection (AHR, 3.04, 95% CI, 1.45-6.37). GIB was associated with increased all-cause mortality (hazard ratio 1.78, 95% CI, 1.39-2.28). GIB is significantly more common in renal transplant recipients than in the general population, and the strongest risk factors are graft loss and African Americans who experience rejection. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. NIH, Organ Transplantat Serv, Walter Reed Army Med Ctr, Washington, DC USA. Walter Reed Army Med Ctr, Gastroenterol & Hepatol Serv, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 27 TC 7 Z9 7 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1121-8428 J9 J NEPHROL JI J. Nephrol. PD JAN-FEB PY 2003 VL 16 IS 1 BP 49 EP 56 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 652AC UT WOS:000181355700007 PM 12649535 ER PT J AU Agnati, LF Franzen, O Ferre, S Leo, G Franco, R Fuxe, K AF Agnati, LF Franzen, O Ferre, S Leo, G Franco, R Fuxe, K TI Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article; Proceedings Paper CT 10th International Winter Conference on Neurodegeneration (IWCN) CY FEB 14-16, 2002 CL SCHLOSS ZIETHEN, GERMANY ID CENTRAL-NERVOUS-SYSTEM; PROTEIN-COUPLED RECEPTORS; DOPAMINE D-2 RECEPTORS; TERM DEPRESSION; SYNAPTIC PLASTICITY; ADENOSINE A(2A); RAT STRIATUM; BINDING CHARACTERISTICS; COGNITIVE NEUROSCIENCE; INTEGRATIVE MECHANISM AB Learning in neuronal networks occurs by instructions to the neurons to change their synaptic weights (i.e., efficacies). According to the present model a molecular mechanism that can contribute to change synaptic weights may be represented by multiple interactions between membrane receptors forming aggregates (receptor mosaics) via oligomerization at both pre- and post-synaptic level. These assemblies of receptors together with inter alia single receptors, adapter proteins, G-proteins and ion channels form the membrane bound part of a complex three-dimensional (3D) molecular circuit, the cytoplasmic part of which consists especially of protein kinases, protein phosphatases and phosphoproteins. It is suggested that this molecular circuit has the capability to learn and store information. Thus, engram formation will depend on the resetting of 3D molecular circuits via the formation of new receptor mosaics capable of addressing the transduction of the chemical messages impinging on the cell membrane to certain sets of G-proteins. Short-term memory occurs by a transient stabilization of the receptor mosaics producing the appropriate change in the synaptic weight. Engram consolidation (long-term memory) may involve intracellular signals that translocate to the nucleus to cause the activation of immediate early genes and subsequent formation of postulated adapter proteins which stabilize the receptor mosaics with the formation of long-lived heteromeric receptor complexes. The receptor mosaic hypothesis of the engram formation has been formulated in agreement with the Hebbian rule and gives a novel molecular basis for it by postulating that the pre-synaptic activity change in transmitter and modulator release reorganizes the receptor mosaics at post-synaptic level and subsequently at pre-synaptic level with the formation of novel 3D molecular circuits leading to a different integration of chemical signals impinging on pre- and post-synaptic membranes hence leading to a new value of the synaptic weight. Engram retrieval is brought about by the scanning of the target networks by the highly divergent arousal systems. Hence, a continuous reverberating process occurs both at the level of the neural networks as well as at the level of the 3D molecular circuits within each neuron of the network until the appropriate tuning of the synaptic weights is obtained and, subsequently, the reappearance of the engram occurs. Learning and memory in the basal ganglia is discussed in the frame of the present hypothesis. It is proposed that formation of long-term memories (consolidated receptor mosaics) in the plasma membranes of the striosomal GABA neurons may play a major role in the motivational learning of motor skills of relevance for survival. In conclusion, long-lived heteromeric receptor complexes of high order may be crucial for learning, memory and retrieval processes, where extensive reciprocal feedback loops give rise to coherent synchronized neural activity (binding) essential for a sophisticated information handling by the central nervous system. C1 Dept Biomed Sci, I-41100 Modena, Italy. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. NIDA, Behav Neurosci Branch, IRP,NIH, US Dept HHS, Baltimore, MD USA. Univ Barcelona Marti & Franques, Dept Biochem, Barcelona, Spain. Dept Rehabil, Ludes Paradiso, Switzerland. RP Agnati, LF (reprint author), Dept Biomed Sci, Via Campi 287, I-41100 Modena, Italy. RI Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015 OI Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919 NR 103 TC 33 Z9 34 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 2003 IS 65 BP 1 EP 28 PG 28 WC Neurosciences SC Neurosciences & Neurology GA 713MQ UT WOS:000184862400002 PM 12946046 ER PT J AU Sokolov, BP Polesskaya, OO Uhl, GR AF Sokolov, BP Polesskaya, OO Uhl, GR TI Mouse brain gene expression changes after acute and chronic amphetamine SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE heat shock protein; neuroplasticity; psychostimulant transcription factors; signal transduction; transcriptional profiling ID RAT NUCLEUS-ACCUMBENS; MESSENGER-RNAS; INJECTION STRESS; CHRONIC COCAINE; HEAT-SHOCK; C-FOS; METHAMPHETAMINE; CORTEX; INDUCTION; DOPAMINE AB Gene expression changes are candidate mechanisms to contribute to long-term consequences of psychostimulant use. We use microarrays to examine the expression of 6340 genes in brains of mice killed 5 or 20 h following 14 day, twice-daily treatments with saline (SS), saline followed by a single 7.5 mg/kg amphetamine dose (SA), or repeated 7.5 mg/kg amphetamine doses (AA) that produce sensitization but no clear-cut neuronal toxicities. Arrays display robust hybridization for about 3600 transcripts. One hundred and seventeen of these expressed transcripts are candidate positives for drug-related changes, displaying >1.8-fold differences from SS control values in whole brains of either SA or AA mice. Five transcripts reveal altered expression in both AA and SA mice. SA mostly enhances expression while AA treatments largely reduce expression. Fourteen. SA and four AA changes in whole brain mRNA were replicated by >1.8-fold changes in independent microarray assessments of either cerebral cortical or brainstem mRNAs, with more changes identified in frontal than in entorhinal/parietal cortical samples. About one-quarter of these changes persist in initial studies of mice killed 20 h after the last amphetamine injection. Each of these genes, including transcription factor, cellular regulatory, structural and other gene family members, are candidates to contribute to brain adaptations to psychostimulants. C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD USA. RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA. NR 23 TC 34 Z9 35 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2003 VL 84 IS 2 BP 244 EP 252 DI 10.1046/j.1471-4159.2003.01523.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 636RL UT WOS:000180470300004 PM 12558987 ER PT J AU Puchowicz, M Tonelli, LH Sternberg, EM AF Puchowicz, M Tonelli, LH Sternberg, EM TI Differential expression of class I MHC mRNA in the hypothalamus of Lewis and Fischer rats SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE lipopolysaccharides; circumventricular organs; paraventricular nucleus; retrochiasmatic area; HPA-axis; inbred rats ID CORTICOTROPIN-RELEASING HORMONE; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; NEURAL ACTIVITY; SPRAGUE-DAWLEY; BRAIN; TRANSCRIPTION; ACTIVATION; RECEPTOR; NEURONS AB The expression of class I major histocompatibility complex (MHC) mRNA was compared in the brains of inflammatory susceptible, hypothalamic-pituitary-adrenal (HPA)-axis blunted Lewis rats and inflammatory resistant, HPA-axis hyperresponsive Fischer rats by quantitative in situ hybridization following lipopolysaccharide (LPS) or vehicle administration. Lewis rats showed lower levels of class I MHC in the hypothalamic paraventricular nucleus (PVN) and retrochiasmatic area (RCA) compared to Fischer rats under both vehicle and LPS conditions. No differences were detected in other brain structures. Differential class I MHC expression in Lewis rats suggests an alteration in mechanisms related to cellular activity of neuroendocrine cells rather than alterations specific to neuroendocrine molecules. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIMH, Integrat Neural Immune Program, SNIB, DHHS,NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, SNIB, DHHS,NIH, 36 Convent Dr MSC 4020,Bldg 36,Room 1A23, Bethesda, MD 20892 USA. NR 42 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2003 VL 134 IS 1-2 BP 35 EP 43 AR PII S0165-5728(02)00421-6 DI 10.1016/S0165-5728(02)00421-6 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 637JV UT WOS:000180508700004 PM 12507770 ER PT J AU Poussin, MA Fuller, CL Goluszko, E Reyes, VE Braciale, VL Christadoss, P AF Poussin, MA Fuller, CL Goluszko, E Reyes, VE Braciale, VL Christadoss, P TI Suppressed clinical experimental autoimmune myasthenia gravis in bm12 mice is linked to reduced intracellular calcium mobilization and IL-10 and IFN-gamma release by acetylcholine receptor-specific T cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE myasthenia gravis; class II MHC; autoimmunity; antigen presentation; mouse model; cytokines ID IMMUNE-RESPONSE; MUTATION; EPITOPE; MOUSE; GENE; DIFFERENTIATION; MOLECULES; SEQUENCE; PEPTIDES; SUBSETS AB Class II MHC mutant bm12 mice have an increased resistance to experimental autoimmune myasthenia gravis (EAMG) compared to C57BL/6 mice. In vitro, this relative resistance was mainly associated with a reduced cytokine response to acetylcholine receptor (AChR) and its dominant pathogenic peptide alpha146-162, whereas the response to the epitope alpha111-126 remained intact. Calcium mobilization after stimulation of AChR-immune T cells with AChR or alpha146-162 peptide, but not alpha111-126 peptide, was decreased in bm12 compared to C57BL/6. Thus, the reduced incidence of clinical EAMG in bm12 is linked to lower IFN-gamma and IL-10 release, and intracellular calcium mobilization by alpha146-162-specific T cells. (C) 2002 Published by Elsevier Science B.V. C1 Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Univ Penn, Med Ctr, Dept Microbiol, Philadelphia, PA 19104 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77555 USA. RP Christadoss, P (reprint author), Univ Texas, Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd 3,142 MRB, Galveston, TX 77555 USA. NR 36 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2003 VL 134 IS 1-2 BP 104 EP 110 AR PII S0165-5728(02)00425-3 DI 10.1016/S0165-5728(02)00425-3 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 637JV UT WOS:000180508700011 PM 12507777 ER PT J AU Clay, JR AF Clay, JR TI On the persistent sodium current in squid giant axons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ALKALINE INTRACELLULAR PH; SLOW INACTIVATION; SINGLE-CHANNEL; ACTION-POTENTIALS; MUSCLE MEMBRANE; GATING CURRENTS; NA+ CHANNELS; NEURONS; CONDUCTANCE; OSCILLATIONS AB R. F. Rakowski, D. C. Gadsby, and P. DeWeer have reported a persistent, tetrodotoxin-sensitive sodium ion current (I-NaP) in squid giant axons having a low threshold (-90 mV) and a maximal inward amplitude of -4 muA/cm(2) at -50 mV. This report makes the case that most of I-NaP is attributable to an ion channel mechanism distinct from the classical rapidly activating and inactivating sodium ion current, I-Na, which is also tetrodotoxin sensitive. The analysis of the contribution of I-Na to I-NaP is critically dependent on slow inactivation of I-Na. The results of this gating process reported here demonstrate that inactivation of I-Na is complete in the steady-state for V > -40 mV, thereby making it unlikely that I-NaP in this potential range is attributable to I-Na. Moreover, -90 mV is well below I Na threshold, as demonstrated by the C. A. Vandenberg and F. Bezanilla model of I-Na gating in squid giant axons. Their model predicts a persistent current having a threshold of -60 mV and a peak amplitude of -25 muA/cm(2) at -20 mV. Modulation of this component by the slow inactivation process predicts a persistent current that is finite in the -60- to -40-mV range having a peak amplitude of -1muA/cm(-2) at -50 mV. Subtraction of this current from the I-NaP measurements yields the portion of I-NaP that appears to be attributable to an ion channel mechanism distinct from I-Na. C1 NINDS, Ion Channel Biophys Grp, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. RP NINDS, Ion Channel Biophys Grp, Basic Neurosci Program, NIH, Bldg 36,Rm 4A21, Bethesda, MD 20892 USA. EM jrclay@ninds.nih.gov NR 32 TC 18 Z9 18 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2003 VL 89 IS 1 BP 640 EP 644 DI 10.1152/jn.00652.2002 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 634FL UT WOS:000180329300057 PM 12522209 ER PT J AU Maric, D Maric, I Chang, YH Barker, JL AF Maric, D Maric, I Chang, YH Barker, JL TI Prospective cell sorting of embryonic rat neural stem cells and neuronal and glial progenitors reveals selective effects of basic fibroblast growth factor and epidermal growth factor on self-renewal and differentiation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fluorescence-activated cell sorting; negative selection; positive selection; neural stem cells; lineage-restricted progenitors; growth factors; calcium imaging ID CENTRAL-NERVOUS-SYSTEM; ACTIVATES CALCIUM CHANNELS; C 3T3 FIBROBLASTS; PRECURSOR CELLS; FGF-RECEPTOR; RESTRICTED PRECURSORS; EGF RECEPTOR; MOUSE-BRAIN; PROLIFERATION; EXPRESSION AB We directly isolated neural stem cells and lineage-restricted neuronal and glial progenitors from the embryonic rat telencephalon using a novel strategy of surface labeling and fluorescence-activated cell sorting. Neural stem cells, which did not express surface epitopes characteristic of differentiation or apoptosis, were sorted by negative selection. These cells predominantly expressed fibroblast growth factor receptor type 1 (FGFR-1), and a minority exhibited basic fibroblast growth factor (bFGF), whereas few expressed epidermal growth factor receptor (EGFR) or EGF. Clonal analyses revealed that these cells primarily self-renewed without differentiating in bFGF-containing medium, whereas few survived or expanded in EGF-containing medium. Culturing of neural stem cells in bFGF- and EGF-containing medium permitted both self-renewal and differentiation into neuronal, astroglial, and oligodendroglial phenotypes. In contrast, lineage-restricted progenitors were directly sorted by positive selection using a combination of surface epitopes identifying neuronal or glial phenotypes or both. These cells were also primarily FGFR-1(+), with few EGFR(+), and most expanded and progressed along their expected lineages in bFGF-containing medium but not in EGF-containing medium. Ca2+ imaging of self-renewing neural stem cells cultured in bFGF-containing medium revealed that bFGF, but not EGF, induced cytosolic Ca2+ (Ca-c(2+)) responses in these cells, whereas in bFGF- and EGF-containing medium, both bFGF and EGF evoked Ca-c(2+) signals only in differentiating progeny of these cells. The results demonstrate that bFGF, but not EGF, sustains a calcium-dependent self-renewal of neural stem cells and early expansion of lineage-restricted progenitors, whereas together the two growth factors permit the initial commitment of neural stem cells into neuronal and glial phenotypes. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Maric, D (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Room 4A-24, Bethesda, MD 20892 USA. NR 54 TC 108 Z9 122 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2003 VL 23 IS 1 BP 240 EP 251 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 632BC UT WOS:000180202300030 PM 12514221 ER PT J AU Wanebo, JE Lonser, RR Glenn, GM Oldfield, EH AF Wanebo, JE Lonser, RR Glenn, GM Oldfield, EH TI The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE central nervous system; hemangioblastoma; neoplasm; von Hippel-Lindau disease ID TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; CLINICAL-FEATURES; GROWTH-FACTOR; RADIOSURGERY; IDENTIFICATION; EXPRESSION; RECEPTORS; PHENOTYPE; FAMILIES AB Object. The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel-Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment. Methods. The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts. Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia. The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts. Conclusions. In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect-producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. USN, Ctr Med, Dept Neurosurg, San Diego, CA 92152 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. NR 48 TC 206 Z9 226 U1 2 U2 5 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2003 VL 98 IS 1 BP 82 EP 94 DI 10.3171/jns.2003.98.1.0082 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 636NY UT WOS:000180463700014 PM 12546356 ER PT J AU Weil, RJ Lonser, RR DeVroom, HL Wanebo, JE Oldfield, EH AF Weil, RJ Lonser, RR DeVroom, HL Wanebo, JE Oldfield, EH TI Surgical management of brainstem hemangioblastomas in patients with von Hippel-Lindau disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE tumor suppressor gene; magnetic resonance imaging; microsurgery; stereotactic radiosurgery ID CENTRAL-NERVOUS-SYSTEM; TUMOR-SUPPRESSOR GENE; ENDOLYMPHATIC SAC TUMORS; SPINAL-CORD; GERMLINE MUTATIONS; MEDULLA-OBLONGATA; HEREDITARY CANCER; CLINICAL-FEATURES; STEM; CEREBELLAR AB Object. Hemangioblastomas of the brainstem constitute 5 to 10% of central nervous system (CNS) tumors in patients with von Hippel-Lindau (VHL) disease. At present, optimal management of brainstem hemangioblastomas associated with VHL disease is incompletely defined. In an attempt to clarify some of the uncertainty about the operative treatment of these lesions and its outcome, the authors reviewed all cases of VHL disease in which resection of brainstem hemangioblastomas was performed at the National Institutes of Health during a 10-year period. Methods. Twelve consecutive patients with VHL disease (six male and six female patients [mean age 31.7 +/- 9 years; range 15-46 years]) who underwent 13 operations to remove 17 brainstem hemangioblastomas were included in this study (mean follow-up period, 88.4 +/- 37.4 months; range 37-144 months). Serial examinations, hospital charts, magnetic resonance images, and operative records were reviewed. To evaluate clinical course, clinical grades were assigned to each patient before and after surgery. Preoperative neurological function was the best predictor of long-term outcome. In addition, patients who underwent CNS surgeries for hemangioblastomas were more likely to improve or to remain neurologically stable. Tumor or cyst size, the presence of a cyst, or the location of the tumor (intramedullary, extramedullary, or mixed; posterior medullary, obex, or lateral) did not affect outcome. No patient was neurologically worse after brainstem surgery. At longterm follow-up review (mean 88.4 months), only one patient had declined neurologically and this was due to the cumulative neurological effects caused by eight additional hemangioblastomas of the spinal cord and their surgical treatment. Conclusions. Brainstem hemangioblastomas in patients with VHL disease can be removed safely; they generally should be resected when they become symptomatic or when the tumor has reached a size such that further growth will increase the risks associated with surgery, or in the presence of,an enlarging cyst. Magnetic resonance imaging is usually sufficient for preoperative evaluation and presurgical embolization is unnecessary. The goal of surgery is complete resection of the lesion before the patient experiences a disabling neurological deficit. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Weil, RJ (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D 37, Bethesda, MD 20892 USA. NR 55 TC 62 Z9 69 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2003 VL 98 IS 1 BP 95 EP 105 DI 10.3171/jns.2003.98.1.0095 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 636NY UT WOS:000180463700015 PM 12546357 ER PT J AU Lonser, RR Weil, RJ Wanebo, JE DeVroom, HL Oldfield, EH AF Lonser, RR Weil, RJ Wanebo, JE DeVroom, HL Oldfield, EH TI Surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE hemangioblastoma; microsurgery; spinal cord; syringomyelia; von Hippel-Lindau disease ID CENTRAL-NERVOUS-SYSTEM; INTRAMEDULLARY HEMANGIOBLASTOMA; CLINICAL-FEATURES; TUMORS; GENE AB Object. Von Hippel-Lindau (VHL) disease is an autosomal-dominant disorder frequently associated with hemangioblastomas of the spinal cord. Because of the slow progression, protean nature, and high frequency of multiple spinal hemangioblastomas associated with VHL disease, the surgical management of these lesions is complex. Because prior reports have not identified the factors that predict which patients with spinal cord hemangioblastomas need surgery or what outcomes of this procedure should be expected, the authors have reviewed a series of patients with VHL disease who underwent resection of spinal hemangioblastomas at a single institution to identify features that might guide surgical management of these patients. Methods. Forty-four consecutive patients with VHL disease (26 men and 18 women) who underwent 55 operations with resection of 86 spinal cord hemangioblastomas (mean age at surgery 34 years; range 20-58 years) at the National Institutes of Health were included in this study (mean clinical follow up 44 months). Patient examination, review of hospital charts, operative findings, and magnetic resonance imaging studies were used to analyze surgical management and its outcome. To evaluate the clinical course, clinical grades were assigned to patients before and after surgery. Preoperative neurological status, tumor size, and tumor location were predictive of postoperative outcome. Patients with no or minimal preoperative neurological dysfunction, with lesions smaller than 500 mm(3), and with dorsal lesions were more likely to have no or minimal neurological impairment. Syrinx resolution was the result of tumor removal and was not influenced by whether the syrinx cavity was entered. Conclusions. Spinal cord hemangioblastomas can be safely removed in the majority of patients with VHL disease. Generally in these patients, hemangioblastomas of the spinal cord should be removed when they produce symptoms or signs. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. NR 29 TC 96 Z9 101 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2003 VL 98 IS 1 BP 106 EP 116 DI 10.3171/jns.2003.98.1.0106 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 636NY UT WOS:000180463700016 PM 12546358 ER PT J AU Pluta, RM Iuliano, B DeVroom, HL Nguyen, T Oldfield, EH AF Pluta, RM Iuliano, B DeVroom, HL Nguyen, T Oldfield, EH TI Comparison of anterior and posterior surgical approaches in the treatment of ventral spinal hemangioblastomas in patients with von Hippel-Lindau disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE von Hippel-Lindau disease; spine; hemangioblastoma ID INTRAMEDULLARY HEMANGIOBLASTOMA; VASCULAR MALFORMATIONS; CORD; FEATURES; TUMORS AB Object. Von Hippel-Lindau (VHL) disease is an autosomal-dominant neoplastic syndrome with manifestations in multiple organs, which is evoked by the deletion or mutation of a tumor suppressor gene on chromosome 3p25. Spinal hemangioblastomas (40% of VHL disease-associated lesions of the central nervous system) arise predominantly in the posterior aspect of the spinal cord and are often associated with an intraspinal cyst. Rarely, the tumor develops in the anterior aspect of the spinal cord. Ventral spinal hemangioblastomas are a surgical challenge because of difficult access and because vessels feeding the tumor originate from the anterior spinal artery. The goal of this study was to clarify whether an anterior or posterior surgical approach is better for management of hemangioblastomas of the ventral spinal cord. Methods. The authors performed a retrospective analysis of clinical outcomes and findings on magnetic resonance (MR) imaging studies in eight patients (two women and six men with a mean age of 34 +/- 15 years) who underwent resection of ventral spinal hemangioblastomas (nine tumors: five cervical and four thoracic). Two surgical approaches were used to resect these tumors. A posterior approach was selected to treat five patients (laminectomy and posterior myelotomy in four patients and the posterolateral approach in one patient); an anterior approach (corpectomy and arthrodesis) was selected to treat the remaining three patients. Immediately after surgery, the ability to ambulate remained unchanged in patients in whom an anterior approach had been performed, but deteriorated significantly in patients in whom a posterior approach had been used, because of motor weakness (four of five patients) and/or proprioceptive sensory loss (three of five patients). This difference in ambulation, despite significant improvements over time among patients in the posterior access group, remained significant 6 months after surgery. In all cases, MR images revealed complete resection of the tumor and in five patients significant or complete resolution of the intramedullary cyst was demonstrated (present in six of eight patients). Conclusions. The outcomes of these eight patients with hemangioblastomas of the ventral spinal cord indicate that both immediate and long-term results are better when an anterior approach is selected for resection. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. NR 29 TC 21 Z9 23 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2003 VL 98 IS 1 BP 117 EP 124 DI 10.3171/jns.2003.98.1.0117 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 636NY UT WOS:000180463700017 PM 12546359 ER PT J AU Oiwa, Y Sanchez-Pernaute, R Harvey-White, J Bankiewicz, KS AF Oiwa, Y Sanchez-Pernaute, R Harvey-White, J Bankiewicz, KS TI Progressive and extensive dopaminergic degeneration induced by convection-enhanced delivery of 6-hydroxydopamine into the rat striatum: a novel rodent model of Parkinson disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE apoptosis; convection-enhanced delivery; drug delivery; neuroprotection regeneration ID NEUROTROPHIC FACTOR; SUBSTANTIA-NIGRA; NIGROSTRIATAL PATHWAY; EXCITOTOXIC INJURY; TIME-COURSE; CELL-DEATH; IN-VIVO; NEURONS; APOPTOSIS; LESIONS AB Object. A striatal dopamine lesion induces progressive nigral degeneration in rodents; however, intrastriatal injection of 6-hydroxydopamine (6-OHDA) causes only limited lesions due to spontaneous regeneration of the neurons that survive. To make an extensive lesion, the authors used a convection-enhanced delivery (CED) method for intrastriatal infusion of 6-OHDA and evaluated the animals for a model of Parkinson disease (PD). Methods. Different doses of 6-OHDA were infused into the unilateral striatum in rats by using the CED method. The dopaminergic neuronal degeneration was evaluated based on morphological, biochemical, and behavioral measurements until 8 weeks postlesion. Due to the wide distribution of the drug, CED of 20 mug of 6-OHDA into the striatum was sufficient to obtain a progressive and extensive nigrostriatal lesion as defined by morphological (> 80% cell loss in the substantia nigra [SN]) and biochemical (> 95% decrease in striatal dopamine) criteria. The extent of the lesion manifested as a stable turning behavior with amphetamine (> 6 turns/minute) and apomorphine (> 4 turns/minute). It also appeared that at I week postlesion the apoptotic markers were maximal in neurons of the SN. Conclusions. A rat model of PD with a progressive and extensive dopamine lesion was successfully made by intrastriatal CED of 6-OHDA. In this model, the therapeutic value can be assessed using behavioral, biochemical, and histochemical measurements. The delay of nigral neuronal death with respect to the time of 6-OHDA administration may provide a therapeutic window for testing neuroprotective strategies. C1 NINDS, Mol Therapeut Sect, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Oiwa, Y (reprint author), Wakayama Med Univ, Dept Neurol Surg, Kimiidera,81101, Wakayama 6410012, Japan. RI Kipke, Daryl/A-2167-2009 NR 37 TC 25 Z9 26 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2003 VL 98 IS 1 BP 136 EP 144 DI 10.3171/jns.2003.98.1.0136 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 636NY UT WOS:000180463700020 PM 12546362 ER PT J AU Joseph, J Major, EO AF Joseph, J Major, EO TI Basic, clinical, and epidemiological studies of progressive multifocal leukoencephalopathy: Implications for therapy SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material C1 NIMH, Ctr Mental Hlth Res AIDS, Neurovirol Genet & Mol Therapeut Program, Bethesda, MD 20892 USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Joseph, J (reprint author), NIMH, Ctr Mental Hlth Res AIDS, Neurovirol Genet & Mol Therapeut Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2003 VL 9 SU 1 BP 1 EP 2 DI 10.1080/13550280390195414 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 677FF UT WOS:000182795700001 PM 12709863 ER PT J AU Major, EO Khalili, K AF Major, EO Khalili, K TI Gerald L Stoner (1943-2002) - Obituary SO JOURNAL OF NEUROVIROLOGY LA English DT Biographical-Item C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Temple Univ, Ctr Neurovirol & Canc Biol, Philadelphia, PA 19122 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2003 VL 9 SU 1 BP 93 EP 93 DI 10.1080/13550280390195748 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 677FF UT WOS:000182795700017 ER PT J AU Dean, D AF Dean, D TI A year of organization for NIBIB SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 NIBIB, Bethesda, MD USA. RP Dean, D (reprint author), NIBIB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2003 VL 44 IS 1 BP 31N EP 31N PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 633HJ UT WOS:000180276500011 ER PT J AU Keusch, GT AF Keusch, GT TI The history of nutrition: Malnutrition, infection and immunity SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2002 Meeting CY APR 20-24, 2002 CL NEW ORLEANS, LOUISIANA DE malnutrition; protein-energy malnutrition; micronutrients; immune system; cell-mediated immunity; humoral immunity; complement system; host defense mechanisms; infectious diseases AB The relationship between nutritional status and the immune system has been a topic of study for much of the 20th century. Dramatic increases in our understanding of the organization of the immune system and the factors that regulate immune function have demonstrated a remarkable and close concordance between host nutritional status and immunity. This report traces the increasing sophistication of our understanding of these relationships and their impact on susceptibility to infection through six stages to the present time. The cyclical relationship between poor nutrition, increased susceptibility to infectious diseases, leading to immunological dysfunction and metabolic responses that further alter nutritional status is described and, wherever possible, related to physiological mechanisms. In addition, the particular role of Nevin Scrimshaw in guiding the progress over the past 50 y is discussed. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Keusch, GT (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 94 Z9 103 U1 0 U2 14 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2003 VL 133 IS 1 BP 336S EP 340S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 633VV UT WOS:000180305900066 PM 12514322 ER PT J AU Sang, CN Max, MB Gracely, RH AF Sang, CN Max, MB Gracely, RH TI Stability and reliability of detection thresholds for human A-beta and A-Delta sensory afferents determined by cutaneous electrical stimulation SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE electric stimulation; pain threshold; pain measurement; sensory thresholds; primary afferent; hyperesthesia ID PAIN; HYPERSENSITIVITY; INFLAMMATION; ANTAGONIST; ALLODYNIA; REFLEX AB Activity in primary afferent fibers that usually mediate fine touch can evoke sensations of pain in conditions in which there is sensitization of central neurons. Input from these large diameter Abeta afferents may also sustain and exacerbate these central mechanisms. The role of these fibers in clinical pain syndromes can be evaluated by applications of electrical stimuli that preferentially activate Abeta axons. This study assessed the stability and reliability of a method of electrical stimulation (ES) useful for clinical evaluation. Monopolar constant current rectangular pulses were delivered to 5 equi-spaced sites on the volar aspect of the left forearm along a transverse line 5 cm, distal to the antecubital crease. Current intensity was gradually increased to determine detection threshold and pain detection threshold. This study determined: 1) Effect of pulse duration (1, 2, and 5 msec); 2) the variation of detection threshold and pain threshold over repeated stimulation; 3) the effect of electrode position with respect to distance from the trunk of underlying ulnar or median nerves; and 4) the effect of repositioning the electrode on variability of detection threshold and pain threshold. There was no significant variability over time for either detection threshold (DT) or pain threshold (PT) at any of the 3 pulse durations tested. There was also no significant effect on variability of shifting the electrode between sites, nor was there a significant difference in variability between sites when placed either over or adjacent to peripheral nerves. Under simulated clinical conditions of electrode re-positioning, the mean detection threshold in 300 trials and ten subjects was 0.30 mA with an overall standard error of 0.007, standard errors of 0.014 over the 10 subjects, 0.003 over the 6 trials, and 0.012 over the 5 locations. Similarly, mean pain threshold in these 300 trials was 3.24 +/- 0.093, with standard errors of 0.12 over the 10 subjects, 0.023 over the 6 trials, and 0.13 over the 5 locations. Mean ratio of pain threshold divided by detection threshold ratio was 10.9 +/- 0.25 with a range of 2.0-28.3. Single pulse, constant current electrical stimulation of the skin at threshold levels is a quantifiable and reliable sensory method that is repeatable within and between testing sessions. Our results suggest that in skin unaffected by allodynia, a ratio of the two sensory thresholds (pain threshold and detection threshold) of less than 2.0 is uncommon. We propose that, in the presence of mechanical allodynia, a pain threshold/detection threshold of less than 2.0 suggests that altered central nervous system processing of Ap input may contribute to allodynia. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier. All rights reserved. C1 Harvard Univ, Dept Anesthesia, Clin 3, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. US Dept Hlth & Human Serv, Natl Inst Dent Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD USA. RP Sang, CN (reprint author), Harvard Univ, Dept Anesthesia, Clin 3, Sch Med,Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 38 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JAN PY 2003 VL 25 IS 1 BP 64 EP 73 AR PII S0885-3924(02)00541-9 DI 10.1016/S0885-3924(02)00541-9 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 640XZ UT WOS:000180715400012 PM 12565190 ER PT J AU Soza, A Lau, DTY Khokhar, MF Conjeevaram, H Park, Y Hoofnagle, JH AF Soza, A Lau, DTY Khokhar, MF Conjeevaram, H Park, Y Hoofnagle, JH TI Resolution of chronic hepatitis B-associated autoimmune neutropenia with interferon-alpha therapy SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID VIRAL-HEPATITIS; VIRUS; DIAGNOSIS; TRIAL C1 NIDDK, Liver Dis Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Soza, A (reprint author), NIDDK, Liver Dis Sect, Digest Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 9B16, Bethesda, MD 20892 USA. RI Soza, Alejandro/C-2907-2009 NR 20 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JAN PY 2003 VL 36 IS 1 BP 141 EP 143 DI 10.1097/00005176-200301000-00027 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 631AC UT WOS:000180143400025 PM 12500011 ER PT J AU Capparelli, EV Mirochnick, M Dankner, WM Blanchard, S Mofenson, L McSherry, GD Gay, H Ciupak, G Smith, B Connor, JD AF Capparelli, EV Mirochnick, M Dankner, WM Blanchard, S Mofenson, L McSherry, GD Gay, H Ciupak, G Smith, B Connor, JD CA Pediat AIDS Clinical Trials Grp TI Pharmacokinetics and tolerance of zidovudine in preterm infants SO JOURNAL OF PEDIATRICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; PERINATAL TRANSMISSION; TYPE-1; INTRAPARTUM; REGIMENS; HIV-1; TRIAL; WOMEN; RISK AB Objective To determine zidovudine pharmacokinetics and tolerance in premature human human immunodeficiency virus-exposed infants. Study design Pediatric AIDS Clinical Trials Group Study 331 was a multicentered prospective, open-label study of the use of zidovudine in premature infants. Thirty-eight infants <35 weeks' gestational age, (GA) were studied while receiving zidovudine 1.5 mg/kg every 12 hours until 2 weeks of age, then 2.0 mg/kg every 8 hours until 6 weeks of age. Population pharmacokinetics were evaluated at 1, 2, and 4 weeks' postnatal age; zidovudine doses were adjusted to maintain troughs <3 muM. Results Zidovudine clearance was lower than reported in term infants at similar postnatal ages. Nine premature infants required dose reduction because of high levels (7/19 <30 weeks' and 2/19 greater than or equal to30 weeks' GA). Postnatal age, GA, serum creatinine, and furosemide use independently predicted zidovudine clearance. Zidovudine was generally well tolerated in this high-risk population. Conclusions Zidovudine clearance is greatly reduced in premature infants. We recommend the following zidovudine dosing schedule in this population: 1.5 mg/kg (intravenous) or 2.0 mg/kg (oral) every 12 hours increased to every 8 hours at 2 weeks of age ( greater than or equal to30 weeks' GA) or at 4 weeks (<30 weeks'. GA). C1 Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pharm, La Jolla, CA 92093 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC USA. Frontier Sci & Technol Inc, Chestnut Hill, MA USA. Pediat Adolescent & Maternal AIDS Branch, Amherst, NY USA. NIAID, NICHHD, NIH, Bethesda, MD USA. UMD, New Jersey Med Sch, Dept Pediat, Newark, NJ USA. Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. RP Capparelli, EV (reprint author), Univ Calif San Diego, Dept Pediat, 9500 Gilman Dr 0979, La Jolla, CA 92093 USA. EM ecapparelli@ucsd.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [1 U01AI41089] NR 20 TC 41 Z9 43 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2003 VL 142 IS 1 BP 47 EP 52 DI 10.1067/mpd.2003.35 PG 6 WC Pediatrics SC Pediatrics GA 636YQ UT WOS:000180485200012 PM 12520254 ER PT J AU Park, KH Chaiworapongsa, T Kim, YM Espinoza, J Yoshimatsu, J Edwin, S Gomez, R Yoon, BH Romero, R AF Park, KH Chaiworapongsa, T Kim, YM Espinoza, J Yoshimatsu, J Edwin, S Gomez, R Yoon, BH Romero, R TI Matrix metalloproteinase 3 in parturition, premature rupture of the membranes, and microbial invasion of the amniotic cavity SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE matrix metalloproteinases; microbial invasion of amniotic cavity; parturition; rupture of membranes; stromelysin 1 ID NECROSIS-FACTOR-ALPHA; INTRAAMNIOTIC INFECTION; SYNOVIAL FIBROBLASTS; STROMELYSIN; DEGRADATION; COLLAGENASE; PROCOLLAGENASE; EXPRESSION; INHIBITORS; ACTIVATION AB Objective. Matrix metalloproteinases (MMY's) area family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3. Study design. A cross-sectional study was conducted, which included Women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = S2) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the ammotic cavity and not in labor (n = 26). MMP-3 concentrations in ammotic fluid were measured by a sensitive and specific immunoassay that was validated for ammotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value < 0.05 was considered statistically significant. Results. (1) MMP-3 was detected in 99.5 % (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02).(5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3. Conclusions. (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection. C1 Wayne State Univ, Hutzel Hosp, NICHD,Perinatol Res Branch,NIH, DHHS,Dept OB GYN, Detroit, MI 48201 USA. Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Santiago, Chile. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, NICHD,Perinatol Res Branch,NIH, DHHS,Dept OB GYN, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011; Park, Kyo Hoon/J-5478-2012 NR 46 TC 51 Z9 53 U1 0 U2 7 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2003 VL 31 IS 1 BP 12 EP 22 DI 10.1515/JPM.2003.002 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 654UA UT WOS:000181513400002 PM 12661139 ER PT J AU Tabak, LA AF Tabak, LA TI New directions in dentstry - The role of the National Institute of Dental and Craniofacial Research SO JOURNAL OF PERIODONTOLOGY LA English DT Article ID HUMAN GENOME; MUTATIONS; SEQUENCE C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Tabak, LA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JAN PY 2003 VL 74 IS 1 BP 65 EP 65 DI 10.1902/jop.2003.74.1.65 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 754JY UT WOS:000187314000010 PM 12593598 ER PT J AU Jia, L Wong, H Wang, Y Garza, M Weitman, SD AF Jia, L Wong, H Wang, Y Garza, M Weitman, SD TI Carbendazim: Disposition, cellular permeability, metabolite identification, and pharmacokinetic comparison with its nanoparticle SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE carbendazim; relative bioavailability; tissue distribution; cell permeability; excretion; metabolism; nanoparticle ID LIQUID-CHROMATOGRAPHY; THIOPHANATE METHYL; IN-VITRO; EXTRACTION; TRANSPORT; BENOMYL; CULTURE; CACO-2; MODEL; CELLS AB The purpose of this study was to systematically evaluate the pharmacokinetic profiles of carbendazim, a novel anticancer drug. Carbendazim reached the highest concentrations in stomach and small intestine by 1 h after oral administration (500 mg/kg) to tumor-bearing nude mice. Four hours later, carbendazim in the large intestine reached maximum concentrations, probably because of pH-induced precipitation of the drug in the large intestine. The highest concentrations of carbendazim in well-perfused tissues, solid tumor, and blood ranged from 63 to 164 mug/g by 4 h. The percentage of carbendazim distributed to solid tumor by 4 h was higher than most well-perfused tissues. Carbendazim concentrations in blood were similar to, or somewhat lower than, those in tumor and other tissues. By 24 h post-dosing, carbendazim concentrations in tissues and blood declined to almost basal levels. The total percentage of administered carbendazim eliminated in urine was 25.7%, and in feces 16.6% within 24 h. Carbendazim exhibited fast permeation across Caco-2 and HT-29 carcinoma cell lines with corresponding permeability coefficients 7.74-8.06 x 10(-5) and 6.8-8.42 x 10(-5) (cm/s). The overall plasma protein binding of carbendazim (0.2-125 mug/mL) assessed by ultrafiltration ranged from 60 to 74%. Comparative pharmacokinetics was conducted in rats by high-pressure liquid chromatography to evaluate the relative bioavailability of carbendazim versus its nanoparticle formulation. Carbendazim and its nanoparticle reached T-max at 2.01 and 1.57 h, respectively. The relative bioavailability of nanoparticle carbendazim versus regular carbendazim was 166%. High-pressure liquid chromatography analysis of the rat serum obtained at 20 h after oral dosing revealed a carbendazim metabolite, which was identified by mass spectroscopy analysis as 2-aminobenzimidazole, a hydrolyzed product of carbendazim. Incubation of carbendazim with human and rat liver microsomes produced a metabolite identified by mass spectrometry as 5(6)- or 4(7)-hydroxyl carbendazim. The comprehensive pharmacokinetic information is important to the current clinical investigation of carbendazim. (C) 2002 Wiley-Liss, Inc. C1 Inst Drug Dev, San Antonio, TX 78245 USA. Ilex Oncol Inc, San Antonio, TX 78245 USA. RP Jia, L (reprint author), Natl Canc Inst, EPN Rm 8042,6130 Execut Blvd, Rockville, MD 20852 USA. NR 23 TC 41 Z9 44 U1 1 U2 16 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JAN PY 2003 VL 92 IS 1 BP 161 EP 172 DI 10.1002/jps.10272 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 632CY UT WOS:000180207200020 PM 12486692 ER PT J AU Kitanaka, J Kitanaka, N Wang, XB Uhl, GR Takemura, M AF Kitanaka, J Kitanaka, N Wang, XB Uhl, GR Takemura, M TI Psychostimulant-induced alterations in GNB1 gene expression in rodent brains SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 76th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 24-26, 2003 CL FUKUOKA, JAPAN SP Japanese Pharmacol Soc C1 Hyogo Med Univ, Dept Pharmacol, Nishinomiya, Hyogo 6638501, Japan. NIDA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2003 VL 91 SU 1 BP 121P EP 121P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 676FJ UT WOS:000182740400438 ER PT J AU Kondo, S Inoue, M Usdin, TB Ueda, H AF Kondo, S Inoue, M Usdin, TB Ueda, H TI In vivo role of tuberoinfundibular peptide of 39 residues (TIP39), the endogenous ligand for PTH2 receptor in pain regulation. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 76th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 24-26, 2003 CL FUKUOKA, JAPAN SP Japanese Pharmacol Soc C1 Nagasaki Univ, Grad Sch Biomed Sci, Div Mol Pharmacol, Nagasaki 8528521, Japan. NIMH, Genet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2003 VL 91 SU 1 BP 182P EP 182P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 676FJ UT WOS:000182740400683 ER PT J AU Mizoguchi, H Wu, HE Spaulding, A Narita, M Hall, FS Sora, I Uhl, GR Nagase, H Tseng, LF Sakurada, S AF Mizoguchi, H Wu, HE Spaulding, A Narita, M Hall, FS Sora, I Uhl, GR Nagase, H Tseng, LF Sakurada, S TI Antagonistic property of buprenorphine for epsilon-opioid receptor. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 76th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 24-26, 2003 CL FUKUOKA, JAPAN SP Japanese Pharmacol Soc C1 Tohoku Pharm Univ, Dept Physiol Anat, Sendai, Miyagi 9818558, Japan. Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. Hoshi Univ, Dept Toxicol, Tokyo 1428501, Japan. NIDA, NIH, Baltimore, MD 21224 USA. Tohoku Univ, Grad Sch Med, Dept Neurosci, Sendai, Miyagi 9808574, Japan. Toray Industries Ltd, Pharm Res Lab, Kamakura, Kanagawa 2488555, Japan. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2003 VL 91 SU 1 BP 218P EP 218P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 676FJ UT WOS:000182740400826 ER PT J AU Kumagai, K Kitayama, S Morioka, N Morita, K Lin, ZC Uhl, GR Dohi, T AF Kumagai, K Kitayama, S Morioka, N Morita, K Lin, ZC Uhl, GR Dohi, T TI Structure-function relationship of dopamine transporter: proline mutations differentially affect the uptake of dopamine and parkinsonism-inducing neurotoxin MPP+. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 76th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 24-26, 2003 CL FUKUOKA, JAPAN SP Japanese Pharmacol Soc C1 Hiroshima Univ, Grad Sch Biomed Sci, Dept Dent Pharmacol, Hiroshima 7348553, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Dent Pharmacol, Okayama 7008525, Japan. NIDA, IRP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2003 VL 91 SU 1 BP 225P EP 225P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 676FJ UT WOS:000182740400853 ER PT J AU Koshimizu, T He, ML Ueno, S Tanoue, A Yanagihara, N Stojilkovic, SS Tsujimoto, G AF Koshimizu, T He, ML Ueno, S Tanoue, A Yanagihara, N Stojilkovic, SS Tsujimoto, G TI Novel splicing variant of mouse P2X2 receptors revealed C-terminal structure-dependent expression and desensitization of P2X receptors. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 76th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 24-26, 2003 CL FUKUOKA, JAPAN SP Japanese Pharmacol Soc C1 Natl Res Inst Child Hlth, Dept Mol Cell Pharmacol, Tokyo 1548509, Japan. NICHD, ERRB, NIH, Bethesda, MD 20892 USA. Univ Occupat & Environm Hlth, Sch Med, Dept Pharmacol, Kitakyushu, Fukuoka 8078555, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2003 VL 91 SU 1 BP 235P EP 235P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 676FJ UT WOS:000182740400896 ER PT J AU Liu, B Hong, JS AF Liu, B Hong, JS TI Role of microglia in inflammation-mediated neurodegenerative diseases: Mechanisms and strategies for therapeutic intervention SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; NECROSIS-FACTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; INDUCED NITRIC-OXIDE; ALZHEIMERS-DISEASE; DOPAMINERGIC NEURODEGENERATION; INTRANIGRAL INJECTION; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; GLIAL RESPONSES AB Evidence from postmortem analysis implicates the involvement of microglia in the neurodegenerative process of several degenerative neurological diseases, including Alzheimer's disease and Parkinson's disease. It remains to be determined, however, whether microglial activation plays a role in the initiation stage of disease progression or occurs merely as a response to neuronal death. Activated microglia secrete a variety of proinflammatory and neurotoxic factors that are believed to induce and/or exacerbate neurodegeneration. In this article, we summarize recent advances on the study of the role of microglia based on findings from animal and cell culture models in the pathogenesis of neurodegenerative diseases, with particular emphasis on Parkinson's disease. In addition, we also discuss novel approaches to potential therapeutic strategies. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, B (reprint author), POB 12233,F1-01, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 59 TC 634 Z9 674 U1 9 U2 53 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2003 VL 304 IS 1 BP 1 EP 7 DI 10.1124/jpet.102.035048 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 626UR UT WOS:000179892200001 PM 12490568 ER PT J AU Venkatesh, B Ramasamy, S Asokan, R Rifkind, JM Manoharan, PT AF Venkatesh, B Ramasamy, S Asokan, R Rifkind, JM Manoharan, PT TI pH influenced metal ion coordination changes in reconstituted hemoglobin SO JOURNAL OF PORPHYRINS AND PHTHALOCYANINES LA English DT Article DE heme; heme proteins; hemoglobin; reconstituted hemoglobin; EPR ID ACID DENATURATION; HYBRID HEMOGLOBINS; FERRIHEMOGLOBINS; METHEMOGLOBIN; SUBUNITS; KINETICS; OXYGEN; CARBONYLHEMOGLOBIN; DISSOCIATION; RESONANCE AB This paper covers a detailed analysis of the coordination changes taking place at the active sites in both Cu and Ni reconstituted hemoglobin as a function of pH. These experiments provide insight into how proteins are held in their native configuration. The EPR results of CuHb reveal that the species formed in extreme acidic condition were different from those formed at extreme basic condition. At pH 3 we see an isotropic spectrum characteristic of 4-coordinated species, while at pH 12 there is an indication of equilibrium between mixtures of species. Further support for the above coordination changes is obtained from FT-Raman of NiHb at different pH conditions. At pH 3 all the 5-coordination marker bands are lost and there is a shift in the 4-coordination marker band, while at pH 12 both 4- and 5-coordination marker bands are still seen with slight shift in their positions. In addition to this, we could see a new peak at 1633 cm(-1). The coordination changes as a function of pH could be seen for both CuHb and NiHb using UV-visible spectroscopic techniques. Copyright (C) 2003 Society of Porphyrins & Phthalocyanines. C1 Indian Inst Technol, Dept Chem, Reg Sophisticated Instrumentat Ctr, Madras 600036, Tamil Nadu, India. NIA, Natl Inst Hlth, Mol Dynam Sect, Baltimore, MD 21224 USA. RP Manoharan, PT (reprint author), Indian Inst Technol, Dept Chem, Reg Sophisticated Instrumentat Ctr, Madras 600036, Tamil Nadu, India. EM ptm@rsic.iitm.ernet.in NR 27 TC 6 Z9 6 U1 1 U2 3 PU SOC PORPHYRINS & PHTHALOCYANINES PI DIJON PA UNIV BOURGOGNE, LIMSAG (U M R 5633), 6 BOULEVARD GABRIEL, 21000 DIJON, FRANCE SN 1088-4246 J9 J PORPHYR PHTHALOCYA JI J. Porphyr. Phthalocyanines PY 2003 VL 7 IS 9-10 BP 637 EP 644 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 815KT UT WOS:000221041900006 ER PT J AU Basrur, V Yang, F Kushimoto, T Higashimoto, Y Yasumoto, K Valencia, J Muller, J Vieira, WD Watabe, H Shabanowitz, J Hearing, VJ Hunt, DF Appella, E AF Basrur, V Yang, F Kushimoto, T Higashimoto, Y Yasumoto, K Valencia, J Muller, J Vieira, WD Watabe, H Shabanowitz, J Hearing, VJ Hunt, DF Appella, E TI Proteomic analysis of early melanosomes: Identification of novel melanosomal proteins SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE melanoma; proteomics; melanosome ID HERMANSKY-PUDLAK-SYNDROME; TYROSINASE-RELATED PROTEIN-1; MONOCLONAL-ANTIBODIES; VESICULAR TRAFFICKING; MASS-SPECTROMETRY; HUMAN MELANOCYTES; MEMBRANE-PROTEIN; MELANOMA-CELLS; BIOGENESIS; EXPRESSION AB Melanin is a heterogeneous biopolymer produced only by specific cells termed melanocytes, which synthesize and deposit the pigment in specialized membrane-bound organelles known as melanosomes. Although melanosomes have been suspected of being closely related to lysosomes and platelets, the total number of melanosomal proteins is still unknown. Thus far, six melanosome-specific proteins have been identified, and the challenge is to characterize the complete proteome of the melanosome to further understand its mechanism of biogenesis. In this report, we used mass spectrometry and subcellular fractionation to identify protein components of early melanosomes. Using this approach, we have identified all 6 of the known melanosome-specific proteins, 56 proteins that are shared with other organelles, and confirmed the presence of 6 novel melanosomal proteins using western blotting and by immunohistochemistry. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B03, Bethesda, MD 20892 USA. RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU NIGMS NIH HHS [GM 37537] NR 72 TC 100 Z9 132 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN-FEB PY 2003 VL 2 IS 1 BP 69 EP 79 DI 10.1021/pr025562r PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 643RN UT WOS:000180874400008 PM 12643545 ER PT J AU Post, RM Luckenbaugh, DA AF Post, RM Luckenbaugh, DA TI Unique design issues in clinical trials of patients with bipolar affective disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE bipolar disorder; clinical trial; crossover; statistics; single case; methodology ID REFRACTORY MOOD DISORDERS; LITHIUM TREATMENT; AFFECTIVE-ILLNESS; MAJOR DEPRESSION; WORKSHOP REPORT; DOUBLE-BLIND; I DISORDER; PLACEBO; LAMOTRIGINE; EFFICACY AB Two National Institute of Mental Health-sponsored meetings of experts on bipolar illness (in 1989 Lind 1994) noted a paucity of clinical psychopharmacological trials in this illness which has now extended over the past two decades. One of the reasons elucidated for this neglect was a lack of agreement in the field as to what constituted an optimal clinical trial design, consequently resulting in low-priority scores for funding of studies in bipolar illness. In this paper, we note some of the characteristics of bipolar illness that make it particularly difficult to study and find such agreed upon trial designs. Some of the assets and liabilities of the well-accepted traditional parallel group, placebo-controlled, randomized clinical trial (RCT) are reviewed, and a series of other potential design options, such as crossover, enrichment, off-on-off-on (B-A-B-A), and N-of-1 trials, are discussed that may help to better address some of the unique clinical characteristics of bipolar illness. Finally, a variety of statistical approaches to analyzing data in off-on-off-on trial designs, and in helping to predetermine necessary durations of clinical trials in individual patients with bipolar disorders, are suggested. Acceptance of a wider variety of clinical trial designs may help facilitate the funding and accelerate the acquisition of new data on treatment of bipolar illness. Published by Elsevier Science Ltd. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Rm 3S239,10 Ctr Dr,MSC-1272, Bethesda, MD 20892 USA. EM robert.post@nih.gov NR 98 TC 19 Z9 19 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JAN-FEB PY 2003 VL 37 IS 1 BP 61 EP 73 AR PII S0022-3956(02)00057-2 DI 10.1016/S0022-3956(02)00057-2 PG 13 WC Psychiatry SC Psychiatry GA 637AP UT WOS:000180489700008 PM 12482471 ER PT J AU Smith, MJ Schmidt, PJ Rubinow, DR AF Smith, MJ Schmidt, PJ Rubinow, DR TI Operationalizing DSM-IV criteria for PMDD: selecting symptomatic and asymptomatic cycles for research SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE premenstrual syndrome; premenstrual dysphoric disorder; symptoms; impairment; diagnosis ID PHASE DYSPHORIC DISORDER; PREMENSTRUAL-SYNDROME AB While diagnostic criteria for premenstrual syndromes (PMS) exist, studies rarely state how these criteria are operationally applied. We examined the consequences of application of different operational methods for DSM-IV criteria for premenstrual dysphoric disorder (PMDD) to individual cycles in women with PMS and controls. PMDD criteria require the presence of both certain types or numbers of symptorris (5/11 symptoms present premenstrually, at least one being one of four mood symptoms) and certain phenomenal characteristics (present premenstrually, absent postmenstrually, causing interference premenstrually). We identified individual cycles as symptomatic or asymptomatic by applying criteria that operationalized the required phenomenal elements of PMDD according to four severity thresholds: literal (i.e. present or absent), 30%, 50%, 70%. Data examined were Daily Rating Form symptom scores from two symptomatic menstrual cycles both in 25 women with PMS and 25 controls. Literal thresholds correctly identified 28% of symptomatic and 4% of asymptomatic cycles, compared with 86 and 70% identification with a 30% threshold, 60 and 86% with a 50% threshold, and 0 and 100% with a 70% threshold. An "optimal" combination of 30% thresholds for premenstrual symptomatology and premenstrual interference and a 50% threshold for postmenstrual symptomatology correctly identified 92% of symptomatic cycles in women with PMS and 72% of asyntptomatic cycles in controls. Different criteria for cycle inclusion yield markedly different sample compositions. No single operational threshold of the phenomenal features maximizes selection of both symptomatic and asymptomatic cycles, largely consequent to the ubiquity of postmenstrual symptoms and premenstrual "interference" even in women without PMS. At the very least, the method for operationalizing DSM-IV criteria should be described in studies of PMDD. Published by Elsevier Science Ltd. C1 NIMH, Behav Endocirnol Branch, Bethesda, MD 20892 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocirnol Branch, Bldg 10,Room 3N238,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. NR 16 TC 29 Z9 31 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JAN-FEB PY 2003 VL 37 IS 1 BP 75 EP 83 AR PII S0022-3956(02)00053-5 DI 10.1016/S0022-3956(02)00053-5 PG 9 WC Psychiatry SC Psychiatry GA 637AP UT WOS:000180489700009 PM 12482472 ER PT J AU Ruiz-Padial, E Martin, JLM Ruiz, SR Vila, J Thayer, J AF Ruiz-Padial, E Martin, JLM Ruiz, SR Vila, J Thayer, J TI Emotional modulated startle and heart rate variability SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Jaen, Jaen, Spain. Univ Granada, E-18071 Granada, Spain. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2003 VL 17 IS 1 BP 42 EP 42 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 693MD UT WOS:000183720600017 ER PT J AU Babiloni, C Babiloni, F Carducci, F Cincotti, F Del Percio, C Hallett, M Kelso, AJS Moretti, DV Liepert, J Rossini, PM AF Babiloni, C Babiloni, F Carducci, F Cincotti, F Del Percio, C Hallett, M Kelso, AJS Moretti, DV Liepert, J Rossini, PM TI Shall I move my right or my left hand? - An EEG study in frequency and time domains SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE motor control; mirror movements; human cortex; movement-related potentials (MRPs); event-related desynchronization/synchronization (ERD/ERS) ID SUPPLEMENTARY MOTOR AREA; EVENT-RELATED DESYNCHRONIZATION; HIGH-RESOLUTION EEG; ELECTROCORTICOGRAPHIC SPECTRAL-ANALYSIS; HUMAN SENSORIMOTOR CORTEX; CENTRAL BETA-RHYTHMS; CEREBRAL-BLOOD-FLOW; CORTICAL POTENTIALS; VOLUNTARY MOVEMENT; CORTICOSPINAL EXCITABILITY AB Event-related desynchronization/synchronization (ERD/ERS) at alpha (10 Hz), beta (20 Hz), and gamma (40 Hz) bands and movement-related potentials (MRPs) were investigated in right-handed subjects who were "free" to decide the side of unilateral finger movements ("fixed" side as a control). As a novelty, this "multi-modal" EEG analysis was combined with the evaluation of involuntary mirror movements, taken as an index of "bimanual competition." A main issue was whether the decision regarding the hand to be moved ("free" movements) could modulate ERD/ERS or MRPs overlying sensorimotor cortical areas typically involved in bimanual tasks. Compared to "fixed" movements, "free" movements induced the following effects: (1) more involuntary mirror movements discarded from EEG analysis; (2) stronger vertex MRPs (right motor acts); (3) a positive correlation between these potentials and the number of involuntary mirror movements; (4) gamma ERS over central areas; and (5) preponderance of postmovement beta ERS over left central area (dominant hemisphere). These results suggest that ERD/ERS and MRPs provide complementary information on the cortical processes belonging to a lateralized motor act. In this context, the results on vertex MRPs would indicate a key role of supplementary/cingulate motor areas not only for bimanual coordination but also for the control of "bimanual competition" and involuntary mirror movements. C1 Univ Roma La Sapienza, Sezione EEG Alta Risoluzione, Dipartimento Fisiol Umana & Farmacol, I-00185 Rome, Italy. IRCCS, I-25123 Brescia, Italy. NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA. Univ Hamburg, Dept Neurol, D-20246 Hamburg, Germany. Neurol Clin, Rome, Italy. CRCCS, Dipartimento Neurol, Osp FBF Isola Tiberina, I-00186 Rome, Italy. RP Babiloni, C (reprint author), Univ Roma La Sapienza, Sezione EEG Alta Risoluzione, Dipartimento Fisiol Umana & Farmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM claudio.babiloni@uniroma1.it RI Rossini, Paolo /D-4994-2013; Moretti, Davide Vito/H-3000-2012; Cincotti, Febo/C-3664-2008; OI Babiloni, Claudio/0000-0002-5245-9839; Rossini, Paolo /0000-0003-2665-534X; Moretti, Davide Vito/0000-0003-0611-1169; Cincotti, Febo/0000-0003-1898-6480; carducci, filippo/0000-0003-4795-0970 NR 80 TC 6 Z9 6 U1 0 U2 4 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2003 VL 17 IS 2 BP 69 EP 86 DI 10.1027//0269-8803.17.2.69 PG 18 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 736RX UT WOS:000186187900002 ER PT J AU Hagemann, D Sollers, JJ Thayer, JF AF Hagemann, D Sollers, JJ Thayer, JF TI Resting frontal brain asymmetry and individual differences in physiological responses to emotional films SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Trier, D-54286 Trier, Germany. NIA, Lab Personal & Cognit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2003 VL 17 IS 3 BP 151 EP 151 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 741YN UT WOS:000186488100060 ER PT J AU Karim, AA Kammer, T Lotze, M Hinterberger, T Godde, B Friedel, E Cohen, L Birbaumer, N AF Karim, AA Kammer, T Lotze, M Hinterberger, T Godde, B Friedel, E Cohen, L Birbaumer, N TI Effects of repetitive transcranial magnetic stimulation (rTMS) on the physiological regulation of cortical excitability SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Tubingen, Tubingen, Germany. Int Max Planck Res Sch Neural & Behav Sci, Tubingen, Germany. Natl Inst Hlth, Bethesda, MD USA. Univ Trent, I-38100 Trent, Italy. RI Karim, Ahmed/D-2503-2009; Kammer, Thomas/K-2168-2012; Godde, Ben/F-5045-2013 OI Kammer, Thomas/0000-0002-2769-5645; Godde, Ben/0000-0001-9101-7286 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2003 VL 17 IS 3 BP 158 EP 158 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 741YN UT WOS:000186488100084 ER PT J AU Buchanan, D Shaw, S Ford, A Singer, M AF Buchanan, D Shaw, S Ford, A Singer, M TI Empirical science meets moral panic: An analysis of the politics of needle exchange SO JOURNAL OF PUBLIC HEALTH POLICY LA English DT Article ID BAN AB The paper presents an analysis of the policy advocacy strategies used by both proponents and opponents of needle exchange programs in the US, drawing on the analytic framework developed by Stone. Based on a case study of the politics of needle exchange in Massachusetts, we argue that proponents of needle exchange have relied almost exclusively on empirical scientific arguments to build their case, while opponents have generally resorted to normative ethical arguments. Since the frames of argument are unrelated, the two sides talk past one another, bypassing progress towards resolution or consensus. By failing to address the ethical concerns raised by opponents, public health advocates of needle exchange are losing the larger public debate. The paper concludes with specific recommendations for how public health advocates should respond to the normative dimensions of this public policy issue. C1 Univ Massachusetts, Sch Publ Hlth, Amherst, NY 10003 USA. Hispan Hlth Council, Hartford, CT 06106 USA. Univ Massachusetts, Dept Publ Policy, Amherst, MA 01003 USA. RP Buchanan, D (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd,Room 2149, Bethesda, MD 20892 USA. EM buchanand@mail.nih.gov FU NIDA NIH HHS [R01 DA12569] NR 50 TC 24 Z9 24 U1 1 U2 6 PU JOURNAL PUBLIC HEALTH POLICY PI S BURLINGTON PA 208 MEADOWOOD DR, S BURLINGTON, VT 05403 USA SN 0197-5897 J9 J PUBLIC HEALTH POL JI J. Public Health Policy PY 2003 VL 24 IS 3-4 BP 427 EP 444 DI 10.2307/3343386 PG 18 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 813KE UT WOS:000220905200017 PM 15015873 ER PT J AU Lukashev, DE Caldwell, CC Chen, P Apasov, SG Margulies, DH Sitkovsky, MV AF Lukashev, DE Caldwell, CC Chen, P Apasov, SG Margulies, DH Sitkovsky, MV TI A serine/threonine phosphorylation site in the ectodomain of a T cell receptor beta chain is required for activation by superantigen SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article DE TCR; ectophosphorylation; cell surface; superantigen ID ANTIGEN RECEPTOR; ECTOPROTEIN KINASES; EFFECTOR FUNCTIONS; ALPHA-CHAIN; C-ALPHA; SURFACE; PROTEINS; SUBUNIT; RECOGNITION; MUTAGENESIS AB The presence of consensus phosphorylation sites in the ectodomains of cell surface proteins suggests that such post-translational modification may be important in regulation of surface receptor activity. To date, the only cell surface receptor for which such ectodomain phosphorylation has been conclusively demonstrated is the clonally expressed T cell antigen receptor (TCR). Attempts to conclusively identify individual phosphorylated residues in TCR alpha and beta chains and determine their functional, significance by biochemical approaches failed due to insufficient quantities of purified molecules. Here we present the. results of an alternative approach where survey of phosphorylation sites in the TCR alpha and beta chains was accomplished using site-directed mutagenesis and retroviral vector expression, as well as in vitro phosphorylation of synthetic peptide substrates. All mutants studied directed the cell surface expression of normal amounts of TCR, and all transfectants could be stimulated to produce IL-2 in response to substrate-immobilized antibody to TCR. However, mutation of serine-88 in the protein kinase A phosphorylation site of the TCR beta chain resulted in a complete lack of response to the superantigen staphylococcal enterotoxin B (SEB). In addition, this mutation abolished TCR-associated tyrosine phosphorylation, consistent with the impairment of cell signaling. Reversion of the serine-88/alanine mutation with phosphorylatable threonine completely restored the SEB recognition by TCR. These results, interpreted in the context of the known three-dimensional structure of the complex of SEB and TCR, are consistent with the view that serine-88 is important for the contact of the TCR beta chain with SEB. C1 NIAID, Immunol Lab, NIH, Biochem & Immunopharmacol Sect, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Mol Biol Sect, Bethesda, MD 20892 USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, Biochem & Immunopharmacol Sect, Bldg,10,Room 11N311, Bethesda, MD 20892 USA. RI Lukashev, Dmitriy/F-8133-2010; Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375; Caldwell, Charles/0000-0003-1692-4550 NR 31 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PY 2003 VL 23 IS 1 BP 33 EP 52 DI 10.1081/RRS-120018759 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 755VZ UT WOS:000187433300003 PM 12680588 ER PT J AU Schetz, JA Kim, OJ Sibley, DR AF Schetz, JA Kim, OJ Sibley, DR TI Pharmacological characterization of mammalian D-1 and D-2 dopamine receptors expressed in Drosophila Schneider-2 cells SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article DE biogenic amine receptor; GPCR; over-expression; insect cell ID FUNCTIONAL-CHARACTERIZATION; FATTY-ACIDS; MELANOGASTER; CLONING; BINDING; K1 AB Mammalian D-1 and D-2 dopamine receptors were stably expressed in Drosophila Schneider-2 (S2) cells and screened for their pharmacological properties. Saturable, dose-dependent, high affinity binding of the D-1-selective antagonist [H-3]SCH-23390 was detected only in membranes from S2 cells induced to express rat dopamine D-1 receptors, while saturable, dose-dependent, high affinity binding of the D-2-selective antagonist [H-3]methylspiperone was detected only in membranes from S2 cells induced to express rat dopamine D-2 receptors. No specific binding of either radioligand could be detected in membranes isolated from uninduced or untransfected S2 cells. Both dopamine D-1 and D-2 receptor subtypes displayed the appropriate stereoselective binding of enantiomers of the nonselective antagonist butaclamol. Each receptor subtype also displayed the appropriate agonist stereoselectivities. The dopamine D-1 receptor bound the (+)-enantiomer of the D-1-selective agonist SKF38393 with higher affinity than the (-)-enantiomer, while the dopamine D-2 receptor bound the (-)-enantiomer of the D-2-selective agonist norpropylapomorphine with higher affinity than the (+)-enantiomer. At both receptor subtypes, dopamine binding was best characterized. as occurring to a single low affinity site. In addition, the low affinity dopamine binding was also found, to be insensitive to GTPgammaS and magnesium ions. Overall, the pharmacological profiles of mammalian dopamine D-1 and D-2 receptors expressed in Drosophila S2 cells is comparable to those observed for these same receptors when they are expressed in mammalian cell lines. A notable distinction is that there is no evidence for the coupling of insect G proteins to mammalian dopamine receptors. These results suggest that the S2 cell insect G system may provide a convenient source. of pharmacologically active mammalian D-1 and D-2 dopamine receptors free of promiscuous G protein contaminants. C1 Univ Mississippi, Dept Pharmacol, University, MS 38677 USA. Natl Inst Neurol Disorders & Stroke, Mol Neuropharmacol Sect, NIH, Bethesda, MD USA. RP Schetz, JA (reprint author), Univ Mississippi, Dept Pharmacol, POB 1848, University, MS 38677 USA. FU NCRR NIH HHS [P20 RR017701, P20 RR017701-02] NR 21 TC 3 Z9 3 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PY 2003 VL 23 IS 1 BP 99 EP 109 DI 10.1081/RRS-120018763 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 755VZ UT WOS:000187433300007 PM 12680592 ER PT J AU Chumlea, WC Dwyer, J Bergen, C Burkart, J Paranandi, L Frydrych, A Cockram, DB Kusek, JW McLeroy, S AF Chumlea, WC Dwyer, J Bergen, C Burkart, J Paranandi, L Frydrych, A Cockram, DB Kusek, JW McLeroy, S CA HEMO Study Grp TI Nutritional status assessed from anthropometric measures in the HEMO study SO JOURNAL OF RENAL NUTRITION LA English DT Article ID MAINTENANCE HEMODIALYSIS-PATIENTS; MORTALITY; MALNUTRITION; AGE AB Objective: Anthropometric methods are screening techniques for assessing nutritional stores of fat and lean tissues among persons with renal disease. This report presents cross-sectional baseline data on anthropometric indicators of nutritional status from a group of hemodialysis patients in a multicenter clinical trial, the Hemodialysis (HEMO) Study. Design: The HEMO Study is a prospective, multicenter, randomized, 2 X 2 factorial clinical trial to evaluate the efficacy of the delivered dose of dialysis, defined by Kt/V, and membrane flux in reducing morbidity and mortality in (maintenance) hemodialysis patients. Standardized measures of weight, stature, body mass index (BMI), arm and calf circumference, and triceps and subscapular skinfolds were taken immediately after dialysis. The analytic methods consisted of univariate statistics, including means, standard deviations, and selected percentiles presented as tables of descriptive statistics. Study findings were compared with corresponding national reference data from the Second National Health and Nutrition Examination Survey (NHANES 11). Patients: Eligible patients between 18 and 80 years of age on chronic hemodialysis for at least 3 months, receiving hemodialysis 3 times per week and with a residual renal clearance of < 1.5 mL/min were examined. Patients also had to be able to attain an eKt/V of greater than or equal to 1.45 in 4.5 hours or an anthropometric volume < 45 to 50 L thus excluding persons with body weights over about 85 kg. The study sample consisted of the first 1,000 randomized patients, 464 men and 536 women; 642 blacks, 318 whites; and 40 of other racial backgrounds out of 1,847 randomized. Results: Differences in nutritional status by sex, race, duration of dialysis, and comorbid disease were found among these patients enrolled in the HEMO Study. In comparison with NHANES 11, these hemodialysis patients were, on average, lighter with less adipose and muscle tissue than healthy persons of the same ages. These findings can be indicators of persons with chronic disease. Those with diabetes were overweight based on their BMI values. Conclusion: These HEMO Study data provide a clinical reference for the use of these anthropometric indicators in assessing the nutritional status of contemporary hemodialysis patients weighing < 85 kg. (C) 2003 by the National Kidney Foundation, Inc. C1 Wright State Univ, Dept Community Hlth, SOM, Lifespan Hlth Res Ctr, Kettering, OH 45420 USA. Vanderbilt Univ, Med Ctr, Clin Trials Ctr, Div Nephrol, Nashville, TN USA. NIDDK, Div Kidney Urol & Hematol Dis, Renal & Urol Clin Trials, Bethesda, MD USA. Abbott Labs, Ross Prod Div, Med Nutr Res & Dev, Columbus, OH USA. Dept Vet Affairs, Westside Med Ctr, Dept Res 151, Chicago, IL USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Wake Forest Univ, Baptist Med Ctr, Dept Internal Med, Nephrol Sect, Winston Salem, NC 27109 USA. Lankenau Hosp, Med Res Ctr, Div Nephrol, Wynnewood, PA USA. Tufts Univ, New England Med Ctr Hosp, Frances Stern Nutr Ctr, Boston, MA 02111 USA. RP Chumlea, WC (reprint author), Wright State Univ, Dept Community Hlth, SOM, Lifespan Hlth Res Ctr, 3171 Res Blvd, Kettering, OH 45420 USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 28 TC 23 Z9 26 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD JAN PY 2003 VL 13 IS 1 BP 31 EP 38 DI 10.1053/jren.2003.50003 PG 8 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 643BA UT WOS:000180841000006 PM 12563621 ER PT J AU Pillemer, S Gulko, P Ligier, S Yarboro, C Gourley, M Goldbach-Mansky, R Siegel, R Hirsch, R Pucino, F Tilley, B Wilder, RL AF Pillemer, S Gulko, P Ligier, S Yarboro, C Gourley, M Goldbach-Mansky, R Siegel, R Hirsch, R Pucino, F Tilley, B Wilder, RL TI Pilot clinical trial of intravenous doxycycline versus placebo for rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; doxycycline; clinical trial ID DOUBLE-BLIND; MINOCYCLINE; TETRACYCLINES; METHOTREXATE; IMPROVEMENT; 2-YEAR AB Objective. To screen for potential efficacy and assess the feasibility of intravenous (IV) doxycycline as a treatment for rheumatoid arthritis (RA). Methods. The study was a (stratified, block) randomized, double blind, 12 week, pilot trial of IV doxycycline 300 mg/day versus identical appearing IV placebo given over 2 It for 14 days. The primary comparison was to a hypothesized placebo rate of 20% as described by Paulus. If a total of 14 consecutive subjects receiving doxycycline treatment did not respond, it would be considered futile to proceed to a Phase III trial. We planned a placebo group of 14 subjects to verify the placebo response rate and estimate sample size required for a definitive Phase III trial, if such a trial was warranted based on the pilot study. American College of Rheumatology (ACR) RA response criteria were used. After 23 subjects entered, the study was closed due to recruitment difficulties. Results. At baseline, mean (SD) tender joint count was 37 (11.9), swollen joint count 30 (9.6), morning stiffness 317 (319) min, and erythrocyte sedimentation rate 72 mm/h (27.5). Randomization resulted in 10 subjects receiving doxycycline and 13 receiving placebo. Treatment was stopped in 8 subjects: in 6, treatment was ineffective (one taking doxycycline, 5 placebo), and in 2, rashes occurred (one taking doxycycline, one placebo). Only one subject met ACR response criteria in the doxycycline group and none in the placebo group. Having no responders in the placebo group was consistent with placebo response rate of 20% or less. Several patients required peripherally inserted central catheters for venous access. Conclusion. The efficacy of IV doxycycline as a treatment for RA could not be ruled out. However, as the-proportion of responders was small, it is unlikely that potential efficacy of IV doxycycline would out weigh potential disadvantages of IV administration. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Res Inst, Manhasset, NY USA. Washington Hosp Ctr, Washington, DC 20010 USA. Med Univ S Carolina, Div Biometry & Epidemiol, Charleston, SC 29425 USA. RP Pillemer, S (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, 10 Center Dr,Room 1N113,MSC 1190, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 21 TC 6 Z9 6 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2003 VL 30 IS 1 BP 41 EP 43 PG 3 WC Rheumatology SC Rheumatology GA 633LW UT WOS:000180285600008 PM 12508388 ER PT J AU Oates, JC Levesque, MC Hobbs, MR Smith, EG Molano, ID Page, GP Hill, BS Weinberg, JB Cooper, GS Gilkeson, GS AF Oates, JC Levesque, MC Hobbs, MR Smith, EG Molano, ID Page, GP Hill, BS Weinberg, JB Cooper, GS Gilkeson, GS TI Nitric oxide synthase 2 promoter Polymorphisms and systemic lupus erythematosus in African-Americans SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE blacks; polymorphism (genetics); microsatellite repeats; promoter regions (genetics); genetic predisposition to disease ID FUNCTIONAL-ANALYSIS; TANZANIAN CHILDREN; DISEASE-ACTIVITY; GENE; MALARIA; SERUM; PEROXYNITRITE; REGION; 3-NITROTYROSINE; DISEQUILIBRIUM AB Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease in which morbidity and-mortality are higher in African-Americans. The etiology of this racial disparity is unknown. A genetic predisposition to enhanced nitric oxide (NO) production may predispose African-Americans to develop SLE and may increase disease severity. We have demonstrated a correlation between NO production and disease activity in SLE. Two polymorphisms in the inducible NO synthasie (NOS2) promoter region (G-954C and CCTTT microsatellite repeat polymorphisms) are associated with improved outcome in some African patients with malaria. This study was designed to determine if these polymorphisms are. associated with SLE. Methods. We assessed the frequency of both the G-954C and CCTTT microsatellite repeat NOS2 promoter polymorphisms in a cohort of patients with SLE and age, sex, and race matched controls in North Carolina and South Carolina. Results. Both polymorphisms were more frequent among African-American female SLE patients when compared with controls (p=0.04 for the,G-954C polymorphism and p=0.03 for the CCTTT-8 repeat polymorphism). Further, the G-954C and CCTTT-8 repeat polymorphisms were in,linkage disequilibriurn (D'=0.89, p=0.0001) among African-American female SLE patients. Conclusion. Altered genetic control of NOS2 transcription may be a risk factor for SLE among African-American females. The extent of linkage disequilibrium between the G-954C and CCTTT-8 repeat NOS2 promoter polymorphisms suggests that they were co-inherited. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC USA. Durham VAMC, Dept Med, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Ctr Arthrit & Rheumat Dis, Concord, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. FU NIAID NIH HHS [AI41764]; NIAMS NIH HHS [AR39162, R01 AR045476, AR45476] NR 48 TC 29 Z9 30 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2003 VL 30 IS 1 BP 60 EP 67 PG 8 WC Rheumatology SC Rheumatology GA 633LW UT WOS:000180285600011 PM 12508391 ER PT J AU Ling, SM Fried, LP Garrett, ES Fan, MY Rantanen, T Bathon, JM AF Ling, SM Fried, LP Garrett, ES Fan, MY Rantanen, T Bathon, JM TI Knee osteoarthritis compromises early mobility function: The Women's Health and Aging Study II SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE knee; osteoarthritis; mobility; function ID OLDER WOMEN; MUSCLE STRENGTH; PHYSICAL-ACTIVITY; OSTEO-ARTHRITIS; UNITED-STATES; NHANES-I; DISABILITY; PAIN; ADULTS; RISK AB Objective. To examine associations between osteoarthritis (OA) of the knee and early functional limitations in a cohort of high-functioning older women, and evaluate the contributions of muscle strength, body weight, and pain severity to these limitations. Methods. Cross sectional analyses were conducted on baseline data of the Women's Health and Aging Study II (WHAS II), an observational study of disability transitions in a cohort of women aged 70-79 upon entry and who were representative of the one-third highest-functioning community-resident women. Standardarized questionnaires and examinations were used to assess knee OA features, medication use, pain severity, knee extensor muscle strength, and body weight. Functional limitation was assessed using validated performance measures and self-report measures of task modification and task difficulty. Results. Sixty-nine women classified as "symptomatic" for knee OA, 48 with "asymptomatic/intermittently symptomatic," knee OA, and 295 with "no knee OA" were included in the final analysis. Despite selection for their high level of self-reported function, performance was slower and task modification was more frequently reported among women with knee OA than women without knee OA. Lower knee extensor strength, higher body weight, and greater pain severity were associated with knee OA, and also with functional limitations. Conclusion. Knee OA appeared to be associated with early functional limitations in this cohort of high-functioning, older, community-resident women. Lower knee extensor strength, higher body weight, and pain severity were closely associated with these limitations. The extent to which modification of these factors attenuates knee OA associated functional decline should be investigated. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Div Rheumatol, Baltimore, MD 21205 USA. Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland. RP Ling, SM (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr,Box 29, Baltimore, MD 21224 USA. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 FU NCRR NIH HHS [RR00722]; NIA NIH HHS [R01 AG1170301A1] NR 38 TC 36 Z9 37 U1 1 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2003 VL 30 IS 1 BP 114 EP 120 PG 7 WC Rheumatology SC Rheumatology GA 633LW UT WOS:000180285600019 PM 12508399 ER PT J AU Simons-Morton, BG Hartos, JL AF Simons-Morton, BG Hartos, JL TI How well do parents manage young driver crash risks? SO JOURNAL OF SAFETY RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Graduated Driver Licensing CY NOV 05-07, 2002 CL CHATHAM, MASSACHUSETTS DE driving risk; young drivers; parenting; parental management ID GRADUATED LICENSING PROGRAM; 16-AND 17-YEAR-OLD DRIVERS; MOTOR-VEHICLE CRASHES; 16-YEAR-OLD DRIVERS; INVOLVEMENT; PASSENGERS; STATES; RESTRICTIONS; TEENAGERS; RATES AB Motor vehicle crashes are extremely high among young drivers during at least the first year of licensure. Crash risks decline with increased experience, but the more newly licensed teenagers drive, the greater their risk exposure. Hence, the dilemma facing policy makers and parents is how to provide young drivers with driving experience without unduly increasing their crash risk. Graduated driver licensing policies serve to delay licensure and then limit exposure to the highest risk conditions after licensure, allowing young drivers to gain experience only under less risky driving conditions. A similar strategy is needed to guide parents. Parents do not appear to appreciate just how risky driving is for novice drivers and tend to exert less control over their teenage children's driving than might be expected. Recent research has demonstrated that simple motivational strategies can persuade parents to adopt driving agreements and impose greater restrictions on early teen driving. (C) 2002 National Safety Council and Elsevier Science Ltd. All rights reserved. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Simons-Morton, BG (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 42 TC 38 Z9 38 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4375 J9 J SAFETY RES JI J. Saf. Res. PD JAN PY 2003 VL 34 IS 1 BP 91 EP 97 DI 10.1016/S0022-4375(02)00085-3 PG 7 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 642DR UT WOS:000180789400013 PM 12535911 ER PT J AU Wu, XW Milne, JLS Borgnia, MJ Rostapshov, AV Subramaniam, S Brooks, BR AF Wu, XW Milne, JLS Borgnia, MJ Rostapshov, AV Subramaniam, S Brooks, BR TI A core-weighted fitting method for docking atomic structures into low-resolution maps: Application to cryo-electron microscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE conformational search; correlation function; cryo-electron microscopy; docking; Monte Carlo; multiprotein complex; single-particle microscopy ID CRYOELECTRON MICROSCOPY; COMPLEX; RECONSTRUCTIONS; TRANSLOCATION; MECHANISM; MODELS; SITUS AB Cryo-electron microscopy of "single particles" is a powerful method to analyze structures of large macromolecular assemblies that are not amenable to investigation by traditional X-ray crystallographic methods. A key step in these studies is to obtain atomic interpretations of multiprotein complexes by fitting atomic structures of individual components into maps obtained from electron microscopic data. Here, we report the use of a "core-weighting" method, combined with a grid-threading Monte Carlo (GTMC) approach for this purpose. The "core" of an individual structure is defined to represent the part where the density distribution is least likely to be altered by other components that comprise the macromolecular assembly of interest. The performance of the method has been evaluated by its ability to determine the correct fit of (i) the alpha-chain of the T-cell receptor variable domain into a simulated map of the alphabeta complex at resolutions between 5 and 40 Angstrom, and (ii) the E2 catalytic domain of the pyruvate dehydrogenase into an experimentally determined map, at 14 Angstrom resolution, of the icosahedral complex formed by 60 copies of this enzyme. Using the X-ray structures of the two test cases as references, we demonstrate that, in contrast to more traditional methods, the combination of the core-weighting method and the grid-threading Monte Carlo approach can identify the correct fit reliably and rapidly from the low-resolution maps that are typical of structures determined with the use of single-particle. electron microscopy. Published by Elsevier Science (USA). C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Wu, XW (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3308,50 S Dr, Bethesda, MD 20892 USA. NR 24 TC 50 Z9 52 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN PY 2003 VL 141 IS 1 BP 63 EP 76 AR PII S1047-8477(02)00570-1 DI 10.1016/S1047-8477(02)00570-1 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 650XN UT WOS:000181289600007 PM 12576021 ER PT J AU Pak, H Gourgiotis, L Chang, WI Guthrie, LC Skarulis, MC Reynolds, JC Merino, MJ Schrump, DS Libutti, SK Alexander, HR Sarlis, NJ AF Pak, H Gourgiotis, L Chang, WI Guthrie, LC Skarulis, MC Reynolds, JC Merino, MJ Schrump, DS Libutti, SK Alexander, HR Sarlis, NJ TI Role of metastasectomy in the management of thyroid carcinoma: The NIH experience SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE metastasis; multimodality therapy; resection; surgery; survival ID LYMPH-NODE METASTASES; PULMONARY METASTASES; SURGICAL-MANAGEMENT; PAPILLARY CARCINOMA; DISTANT METASTASES; PROGNOSTIC FACTORS; BONE METASTASES; FOLLICULAR CARCINOMA; RADIOIODINE THERAPY; RADIOACTIVE IODINE AB Background and Objectives: We studied the impact of metatasectomy on disease outcome in 29 advanced nonmedullary thyroid carcinoma (ThyrCa) patients who were operated on between 1969 and 2001 at NIH to further define its role in the management of this malignancy. Methods: Data were extracted by retrospective chart review. A Kaplan-Meyer survival curve was constructed, and comparative stratification for various parameters was performed. Results: During 47 surgeries, the following lesions were resected from midmediastinum/hila, 17; lung parenchyma, 12; skeleton, 14; kidneys, 2; and brain, 2. All patients received multiple radioiodine (RAI) treatments. External-beam radiotherapy, chemotherapy and other palliative measures were used in selected patients. Six patients (21%) died within 74.7 +/- 54.7 months after the first distant metastasectomy. The outcome of the remaining patients was as follows: complete remission, 3; partial remission, 10; and 10: progressive disease, 10, with a follow-up of 175 patient-years. Metastasectomy led to a decrease of 38% in thyroglobulin levels in 23 patients. Cumulative survival rates were 78.5 +/- 8.4% at 5 years and 50.2 +/- 12.5% at 10 years (mean +/-SEM) after initial distant metastasectomy. Conclusions: Our data show that extensive targeted metastasectomy in the setting of a tertiary center can be beneficial to patients with disseminated ThyrCa with persistent or recurrent distant disease, when used in conjunction with nonsurgical treatment modalities. J. Surg. Oncol. 2003;82:10-18. (C) 2002 Wiley-Liss, Inc. C1 NCI, Surg Branch, NIH, Bethesda, MD USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD USA. NIDDK, DIR, NIH, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDK, DIR, NIH, Bldg 10,Rm 8D12C,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. NR 73 TC 23 Z9 23 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JAN PY 2003 VL 82 IS 1 BP 10 EP 18 DI 10.1002/jso.10189 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 632UB UT WOS:000180240500003 PM 12501164 ER PT J AU Walkup, JT Labellarte, MJ Riddle, MA Pine, D Greenhill, L Klein, R Davies, M Sweeney, M Fu, CF Hack, S Klee, B McCracken, J Bergman, L Piacentini, J March, J Compton, S Robinson, J O'Hara, T Baker, S Vitiello, B Ritz, L Roper, M AF Walkup, JT Labellarte, MJ Riddle, MA Pine, D Greenhill, L Klein, R Davies, M Sweeney, M Fu, CF Hack, S Klee, B McCracken, J Bergman, L Piacentini, J March, J Compton, S Robinson, J O'Hara, T Baker, S Vitiello, B Ritz, L Roper, M CA Res Units Pediat Psychopharmacolog TI Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE anxiety; treatment; pharmacology; moderators; mediators; fluvoxamine ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED TRIAL; SOCIAL PHOBIA; CLINICAL-TRIAL; DOUBLE-BLIND; MAJOR DEPRESSION; EFFICACY; PREDICTORS; SERTRALINE; FLUVOXAMINE AB Objective: To examine whether age, gender, ethnicity, type of anxiety disorder, severity of illness, comorbidity, intellectual level, family income, or parental education may function as moderators, and whether treatment adherence, medication dose, adverse events, or blinded raters guess of treatment assignment may function as mediators of pharmacological treatment effect in children and adolescents with anxiety disorders. Method: The database of a recently reported double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed. With a mixed-model random-effects regression analysis of the Pediatric Anxiety Rating Scale total score, moderators and mediators were searched by testing for a three-way interaction (strata by treatment by time). A two-way interaction (strata by time) identified predictors of treatment outcome. Results: No significant moderators of efficacy were identified, except for lower baseline depression scores, based on parent's (but not child's) report, being associated with greater improvement (p <.001). Patients with social phobia (p <.05) and greater severity of illness (p <.001) were less likely to improve, independently of treatment assignment. Blinded rater's guess of treatment assignment acted as a possible mediator (p <.001), but improvement was attributed to fluvoxamine, regardless of actual treatment assignment. Treatment adherence tended to be associated (p =.05) with improvement. Conclusions: In this exploratory study, patient demographics, illness characteristics, family income, and parental education did not function as moderators of treatment effect. Social phobia and severity of illness predicted less favorable outcome. Attribution analyses indicated that study blindness remained intact. The presence of concomitant depressive symptoms deserves attention in future treatment studies of anxious children. C1 NIMH, Bethesda, MD USA. RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD USA. RI Piacentini, John/C-4645-2011 FU NCRR NIH HHS [M01RR00052]; NIMH NIH HHS [MH01391, N01MH60016, N01MH70010, N01MH60005, MH57503] NR 41 TC 15 Z9 15 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2003 VL 42 IS 1 BP 13 EP 21 DI 10.1097/01.CHI.0000024906.60748.A8 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 629BF UT WOS:000180030000006 PM 12500072 ER PT J AU Sharp, WS Gottesman, RF Greenstein, DK Ebens, CL Rapoport, JL Castellanos, FX AF Sharp, WS Gottesman, RF Greenstein, DK Ebens, CL Rapoport, JL Castellanos, FX TI Monozygotic twins discordant for attention-deficit/hyperactivity disorder: Ascertainment and clinical characteristics SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE monozygotic twins; discordant twins; attention-deficit/hyperactivity disorder; subject ascertainment ID DEFICIT HYPERACTIVITY DISORDER; OBSTETRIC COMPLICATIONS; ADHD; SCHIZOPHRENIA; ENVIRONMENT; PREGNANCY; SCALE; BIAS AB Objective: Nongenetic factors and phenomenology of attention-deficit/hyperactivity disorder (ADHD) were examined In monozygotic (MZ) twin pairs discordant for ADHD. Method: Recruitment included telephone screening (n= 297 pairs), behavioral ratings obtained from parents and teachers (n = 59 pairs), and, finally, in-person assessment (n = 25 pairs; structured classroom observation, diagnostic interview, psychoeducational evaluation, birth record review, establishment of monozygosity, and anatomic brain imaging). Affected twins were further contrasted with previously studied affected singletons. Results: Of the 25 MZ twin pairs qualifying for in-person evaluation, only 10 proved discordant for ADHD. Affected twins were mostly comparable with affected singletons on clinical measures, although fathers' self-ratings of childhood ADHD status were significantly lower in twins than in singletons. Conclusions: Discordance for ADHD in MZ twins appears to be ascribable to greater environmental discordance and decreased familiality. Despite these differences, affected twins were phenotypically comparable with affected singletons. Thus MZ twins discordant for ADHD, while rare, can inform research on the etiology and pathophysiology of this disorder. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Castellanos, FX (reprint author), NYU, Ctr Child Study, 577 1st Ave,CSC 204, New York, NY 10016 USA. NR 28 TC 19 Z9 19 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2003 VL 42 IS 1 BP 93 EP 97 DI 10.1097/01.CHI.0000024903.60748.F4 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 629BF UT WOS:000180030000015 PM 12500081 ER PT J AU Toro, JR Glenn, G Hou, LF Duray, P Clark, B Merino, M Zbar, B Linehan, M Turner, ML AF Toro, JR Glenn, G Hou, LF Duray, P Clark, B Merino, M Zbar, B Linehan, M Turner, ML TI Facial papules, spontaneous pneumothorax, and renal tumors SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID BIRT-HOGG-DUBE; HEREDITARY MULTIPLE FIBROFOLLICULOMAS; INTESTINAL POLYPOSIS; KIDNEY NEOPLASIA; TRICHODISCOMAS; ACROCHORDONS C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Pathol Branch, Bethesda, MD 20892 USA. NCI, Immunobiol Lab, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, 6120 Execut Blvd,Execut Plaza S,Room 7012, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2003 VL 48 IS 1 BP 111 EP 114 DI 10.1067/mjd.2003.67 PG 4 WC Dermatology SC Dermatology GA 634PC UT WOS:000180348600014 PM 12522379 ER PT J AU Hu, PF Seeman, TE Harris, TB Reuben, DB AF Hu, PF Seeman, TE Harris, TB Reuben, DB TI Does inflammation or undernutrition explain the low cholesterol-mortality association in high-functioning older persons? MacArthur studies of successful aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE serum total cholesterol; mortality; inflammation; malnutrition; aging ID LOW SERUM-CHOLESTEROL; CORONARY HEART-DISEASE; FOLLOW-UP; MEN; RISK; HYPOCHOLESTEROLEMIA; MARKERS; PEOPLE; WOMEN; LEVEL AB OBJECTIVES: To explore the effect of inflammation and undernutrition on the association between hypocholesterolemia and higher overall mortality in high-functioning older persons. DESIGN: Prospective cohort study. SETTING: Three U.S. communities. PARTICIPANTS: A cohort of 870 participants from the MacArthur Studies of Successful Aging. MEASUREMENTS: Baseline information was obtained for serum levels of cholesterol, C-reactive protein, interleukin-6, and albumin; body mass index; prevalent medical conditions; health behaviors; and medications. Crude and multivariate logistic regression analyses were used to examine the association between serum total cholesterol levels and 7-year all-cause mortality, while adjusting for potential confounders. RESULTS: In univariate analysis, the risk ratio of low serum total cholesterol level (<169 mg/dL) for 7-year total mortality was 1.90 (95% confidence interval (CI) = 1.18-3.07). The multiple adjusted risk ratios were 1.82 (95% Cl = 1.10-3.00) after controlling for markers of inflammation and nutrition and 1.39 (95% Cl = 0.80-2.40) after adjustment for additional cardiovascular risk factors. Sex was an important confounding variable that contributed to the observed inverse association between low serum cholesterol and overall mortality in univariate analysis. CONCLUSIONS: Hypocholesterolemia is not an independent risk factor for increased overall mortality in high-functioning community-dwelling older men and women. The association between low total cholesterol and high mortality observed in crude analysis is mainly confounded by common cardiovascular risk factors, rather than underlying inflammation or undernutrition. C1 Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Hu, PF (reprint author), Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr Med & Gerontol, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. NR 29 TC 18 Z9 18 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2003 VL 51 IS 1 BP 80 EP 84 DI 10.1034/j.1601-5215.2002.51014.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 635ML UT WOS:000180403200013 PM 12534850 ER PT J AU Sitges, M Jones, M Shiota, T Qin, JX Tsujino, H Bauer, F Kim, YJ Agler, DA Cardon, LA Zetts, AD Panza, JA Thomas, JD AF Sitges, M Jones, M Shiota, T Qin, JX Tsujino, H Bauer, F Kim, YJ Agler, DA Cardon, LA Zetts, AD Panza, JA Thomas, JD TI Real-time three-dimensional color Doppler evaluation of the flow convergence zone for quantification of mitral regurgitation: Validation experimental animal study and initial clinical experience SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID SURFACE-AREA METHOD; ORIFICE AREA; IN-VITRO; 3-DIMENSIONAL RECONSTRUCTION; AORTIC REGURGITATION; ECHOCARDIOGRAPHY; MODEL; JETS; ACCELERATION; INVITRO AB Background: Pitfalls of the flow convergence (FC) method, including 2-dimensional imaging of the 3-dimensional (3D) geometry of the FC surface, can lead to erroneous quantification of mitral regurgitation (MR). This limitation may be mitigated by the use of real-time 3D color Doppler echocardiography (CE). Our objective was to validate a real-time 3D navigation method for MR quantification. Methods: In 12 sheep with surgically induced chronic MR, 37 different hemodynamic conditions were studied with real-time 3DCE. Using real-time 3D navigation, the radius of the largest hemispherical FC zone was located and measured. MR volume was quantified according to the FC method after observing the shape of FC in 3D space. Aortic and mitral electromagnetic flow probes and meters were balanced against each other to determine reference MR volume. As an initial clinical application study, 22 patients with chronic MR were also studied with this real-time 3DCE-FC method. Left ventricular (IV) outflow tract automated cardiac flow measurement (Toshiba Corp, Tokyo, Japan) and real-time 3D IV stroke volume were used to quantify the reference MR volume (MR volume = 3DLV stroke volume automated cardiac flow measurement). Results. In the sheep model, a good correlation and agreement was seen between MR volume by real-time 3DCE and electromagnetic (y = 0.77X + 1.48, r = 0.87, P < .001, Delta = -0.91 +/- 2.65 mL). In patients, real-time 3DCE-derived MR volume also showed a good correlation and agreement with the reference method (y = 0.89x - 0.38, r = 0.93, P < .001, A -4.8 +/- 7.6 mL). Conclusions: real-time 3DCE can capture the entire FC image, permitting geometrical recognition of the FC zone geometry and reliable MR quantification. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cardiovasc Imaging Ctr, Cleveland, OH 44195 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Shiota, T (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, Cardiovasc Imaging Ctr, 9500 Euclid Ave,Desk F-15, Cleveland, OH 44195 USA. NR 29 TC 34 Z9 42 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2003 VL 16 IS 1 BP 38 EP 45 DI 10.1067/mje.2003.37 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 634PR UT WOS:000180350000008 PM 12514633 ER PT J AU Stewart, JH Buccianti, G Agodoa, L Gellert, R McCredie, MRE Lowenfels, AB Disney, APS Wolfe, RA Boyle, P Maisonneuve, P AF Stewart, JH Buccianti, G Agodoa, L Gellert, R McCredie, MRE Lowenfels, AB Disney, APS Wolfe, RA Boyle, P Maisonneuve, P TI Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: Analysis of data from the United States, Europe, and Australia and New Zealand SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID UREMIC PATIENTS; RISK; FAILURE; TRANSPLANTATION; NEOPLASIA; TUMORS AB Patients on maintenance dialysis have increased risk for cancer, especially in the kidney and urinary tract. In a retrospective cohort of 831,804 patients starting dialysis during 1980 to 1994 in the United States, Europe, or Australia and New Zealand, standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for kidney and bladder cancers. Risks for cancers of the kidney (SIR 3.6; CI 3.5 to 3.8) and bladder (SIR 1.5; CI 1.4 to 1.6) were increased, relatively more in younger than older patients and more in female patients (kidney: SIR 4.6, CI 4.3 to 4.9; bladder: SIR 2.7, CI 2.4 to 2.9) than male patients (kidney: SIR 3.2, CI 3.0 to 3.4; bladder: SIR 1.3, CI 1.2 to 1.3). SIR for kidney cancer were raised in all categories of primary renal disease, and for bladder cancer in all but diabetes and familial, hereditary diseases. Notably high SIR occurred in toxic nephropathies (chiefly analgesic nephropathy) and miscellaneous conditions (a category that includes Balkan nephropathy), the excess of kidney cancer in these conditions being urothelial in origin. SIR for kidney cancer rose significantly, and those for bladder cancer fell (not reaching significance) with time on dialysis. There was no association with type of dialysis. The pattern of increased risk for renal parenchymal cancer in dialysis patients is consistent with causation through acquired renal cystic disease and of urothelial cancers of the kidney and bladder with the carcinogenic effects of certain primary renal diseases. C1 Univ Otago, Dept Med & Surg Sci, Dunedin, New Zealand. Osped Bassini, Div Nefrol & Dialisi, Azienda Osped San Gerardo, Cinisello Balsamo, Italy. NIDDKD, Div Kidney Urol & Heamtol Dis, Bethesda, MD 20892 USA. CSK AM Banacha, Dept Internal Med & Nephrol, Warsaw, Poland. Univ Otago, Sch Med, Dept Prevent & Social Med, Dunedin, New Zealand. New York Med Coll, Valhalla, NY 10595 USA. Queen Elizabeth Hosp, ANZDATA Registry, Adelaide, SA, Australia. Univ Michigan, USRDS Coordinating Ctr, Ann Arbor, MI 48109 USA. European Inst Oncol, Div Epidemiol & Biostat, I-20141 Milan, Italy. RP Maisonneuve, P (reprint author), European Inst Oncol, Div Epidemiol & Biostat, Via Ripamonti 435, I-20141 Milan, Italy. RI Gellert, Ryszard/F-4604-2010; Boyle, Peter/A-4380-2014; OI Boyle, Peter/0000-0001-6251-0610; Gellert, Ryszard/0000-0001-9382-0734; Maisonneuve, Patrick/0000-0002-5309-4704 NR 31 TC 130 Z9 135 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2003 VL 14 IS 1 BP 197 EP 207 DI 10.1097/01.ASN.0000039608.81046.81 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 629VR UT WOS:000180072800021 PM 12506152 ER PT J AU Wood, FB Sahali, R Press, N Burroughs, C Mala, TA Siegel, ER Fuller, SS Rambo, N AF Wood, FB Sahali, R Press, N Burroughs, C Mala, TA Siegel, ER Fuller, SS Rambo, N TI Tribal connections health information outreach: results, evaluation, and challenges SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB In 1997, the National Library of Medicine (NLM), a component of the National Institutes of Health (NIH), initiated a program of intensified outreach to Native Americans, initially focusing on the Pacific Northwest in collaboration with the Pacific Northwest Regional Medical Library (PNRML). This initiative, known as the Tribal Connections Project, emphasized the establishment or strengthening of Internet connections at select Indian reservations and Alaska Native villages and related needs assessment and training. The hope was that these efforts would improve tribal access to health information available via the Internet and the Web. Phase I included sixteen tribal sites-eight in Washington, four in Alaska, two in Montana, and one each in Oregon and Idaho. Phase I results indicate that the project was successful in assessing local needs and building awareness of the Internet, forging new partnerships with and between the participating Indian reservations and Alaska Native villages and other organizations, making real improvements in the information technology (IT) infrastructure and Internet connectivity at fifteen of sixteen sites, and conducting training sessions with several hundred tribal participants across thirteen sites. Most importantly, the project demonstrated the key role of tribal community involvement and empowerment and contributed to development of an outreach evaluation field manual and the evolving concept of community-based outreach. The knowledge gained from Tribal Connections Project Phase I is helping refine and enhance subsequent NLM-sponsored tribal connections and similar community outreach efforts. C1 Natl Lib Med, Off Hlth Informat Programs Dev, Bethesda, MD 20894 USA. Univ Washington, Pacific NW Reg Med Lib, Seattle, WA 98195 USA. Mars Hill Grad Sch, Bothell, WA 98021 USA. Southcent Fdn, Anchorage, AK 99508 USA. Assoc Amer Indian Physicians, Oklahoma City, OK 73108 USA. Natl Lib Med, Bethesda, MD 20894 USA. RP Wood, FB (reprint author), Natl Lib Med, Off Hlth Informat Programs Dev, Bethesda, MD 20894 USA. EM fred_wood@nlm.nih.gov; rs@u.washington.edu; pressno@mhgs.net; cburroug@u.washington.edu; tmala@citci.com; siegel@nlm.nih.gov; sfuller@u.washington.edu; nrambo@u.washington.edu OI Rambo, Neil/0000-0003-2376-5121 NR 21 TC 6 Z9 6 U1 1 U2 2 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2003 VL 91 IS 1 BP 57 EP 66 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA 642BN UT WOS:000180784300010 PM 12568158 ER PT J AU Simon, R Radmacher, MD Dobbin, K McShane, LM AF Simon, R Radmacher, MD Dobbin, K McShane, LM TI Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENE-EXPRESSION PROFILES; MOLECULAR CLASSIFICATION; BREAST-CANCER; ADENOCARCINOMA; PREDICTION; LUNG C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Kenyon Coll, Dept Biol, Gambier, OH USA. Kenyon Coll, Dept Math, Gambier, OH USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, NIH, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. NR 22 TC 675 Z9 694 U1 0 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 1 PY 2003 VL 95 IS 1 BP 14 EP 18 PG 5 WC Oncology SC Oncology GA 629YB UT WOS:000180079200007 PM 12509396 ER PT J AU Strickler, HD Goedert, JJ Devesa, SS Lahey, J Fraumeni, JF Rosenberg, PS AF Strickler, HD Goedert, JJ Devesa, SS Lahey, J Fraumeni, JF Rosenberg, PS TI Trends in US pleural mesothelioma incidence rates following simian virus 40 contamination of early poliovirus vaccines SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN BRAIN-TUMORS; LARGE T-ANTIGEN; DNA-SEQUENCES; SV40; SIMIAN-VIRUS-40; EXPOSURE; CANCER; POLYOMAVIRUSES; PATTERNS; CONTAIN AB Background: Poliovirus vaccines that were used during the late 1950s and early 1960s were contaminated with simian virus 40 (SV40), a monkey virus that is tumorigenic in rodents. SV40 DNA sequences have been detected in some human cancers, especially pleural mesotheliomas, although results are conflicting. We examined the relationship between SV40-contaminated poliovirus vaccine exposure and subsequent rates of pleural mesothelioma in the United States. Methods: We used data from the Surveillance, Epidemiology, and End Results Program to estimate age- and sex-specific pleural mesothelioma incidence rates per 105 person-years (py) from 1975 through 1997 and the Poisson distribution to determine 95% confidence intervals (CIs) for each rate. The prevalence, by birth cohort, of poliovirus vaccine exposure during the period of widespread SV40 contamination was determined from published survey data. Trends in mesothelioma incidence rates were assessed by examining age- and sex-specific rates over calendar periods and with the use of the age-period-cohort model. Trends in mesothelioma incidence were then compared with trends in prevalence of exposure. All statistical tests were two-sided. Results: The age-standardized pleural mesothelioma incidence rate for 1975 through 1997 was 1.29/10(5) py (95% CI = 1.24/10(5) to 1.34/10(5) py) in males and 0.21/10(5) py (95% CI = 0.20/10(5) to 0.23/10(5) py) in females. The rate in males increased from 0.79/10(5) py (95 % CI = 0.62/10(5) to 1.0/10(5) py) in 1975 to a peak of 1.69/10(5) py (95 % CI = 1.46/10(5) to 1.95/10(5) py) in 1992. Incidence rates increased the most among males who were 75 years of age or older, the age group least likely to have been immunized against poliovirus. Incidence rates among males in the age groups most heavily exposed to SV40-contaminated poliovirus vaccine remained stable or decreased from 1975 through 1997. Similar age-specific trends were observed among females. The age-period-cohort models for men and women also indicated that the trends in pleural mesothelioma incidence were not related to trends in exposure to SV40-contaminated poliovirus vaccine. Conclusions: Age-specific trends in U.S. pleural mesothelioma incidence rates are not consistent with an effect of exposure to SV40-contaminated poliovirus vaccine. Nonetheless, given reports of the detection of SV40 genomic DNA sequences in human mesotheliomas, monitoring of vaccine-exposed cohorts should continue. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Strickler, HD (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, 1300 Morris Pk Ave,Belfer 1308, Bronx, NY 10461 USA. FU NCI NIH HHS [CA13330] NR 40 TC 37 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 1 PY 2003 VL 95 IS 1 BP 38 EP 45 PG 8 WC Oncology SC Oncology GA 629YB UT WOS:000180079200010 PM 12509399 ER PT J AU Sherman, ME Lorincz, AT Scott, DR Wacholder, S Castle, PE Glass, AG Mielzynska-Lohnas, I Rush, BB Schiffman, M AF Sherman, ME Lorincz, AT Scott, DR Wacholder, S Castle, PE Glass, AG Mielzynska-Lohnas, I Rush, BB Schiffman, M TI Baseline cytology, human papillomavirus testing, and risk for cervical neoplasia: A 10-year cohort analysis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CARCINOMA IN-SITU; NATURAL-HISTORY; INTRAEPITHELIAL NEOPLASIA; PAPANICOLAOU TEST; YOUNG-WOMEN; INFECTION; CANCER; HPV; PREVALENCE; LESIONS AB Background: Annual Pap smear screening has been favored over less frequent screening in the United States to minimize the risk of cervical cancer. We evaluated whether simultaneous screening with a Pap test and human papillomavirus (HPV) testing is useful for assessing the risk for cervical intraepithelial neoplasia (CIN) 3 or cervical cancer. Methods: We enrolled 23 702 subjects in a study of HPV infection at Kaiser Permanente, Northwest Division, Portland, OR. Data were analyzed for 20810 volunteers who were at least 16 years old (mean = 35.9 years) with satisfactory baseline Pap tests and suitable samples for HPV testing. Women were followed for up to 122 months (from April 1, 1989, to June 30, 1999) to determine the risk for histopathologically confirmed CIN3 or cancer. Results: Among 171 women with CIN3 or cancer diagnosed over 122 months, 123 (71.9%, 95% confidence interval [CI] = 65.2% to 78.7%) had baseline Pap results of atypical squamous cells or worse and/or a positive HPV test, including 102 (86.4%, 95% CI = 80.3% to 92.6%) of the 118 cases diagnosed within the first 45 months of follow-up. During this 45-month period, the cumulative incidence of CIN3 or cancer was 4.54% (95% CI = 3.61% to 5.46%) among women with a Pap test result of atypical squamous cells or worse, positive HPV tests, or both compared with 0.16% (95% CI = 0.08% to 0.24%) among women with negative Pap and HPV tests. Age, screening behavior, a history of cervical cancer precursors, and a history of treatment for CIN minimally affected results. Conclusions: Negative baseline Pap and HPV tests were associated with a low risk for CIN3 or cancer in the subsequent 45 months, largely because a negative HPV test was associated with a decreased risk of cervical neoplasia. Negative combined test results should provide added reassurance for lengthening the screening interval among low-risk women, whereas positive results identify a relatively small subgroup that requires more frequent surveillance. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Digene Corp, Gaithersburg, MD USA. Kaiser Permanente NW Div, Portland, OR USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,Rm 7080, Bethesda, MD 20892 USA. NR 30 TC 281 Z9 315 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 1 PY 2003 VL 95 IS 1 BP 46 EP 52 PG 7 WC Oncology SC Oncology GA 629YB UT WOS:000180079200011 PM 12509400 ER PT J AU Hsing, AW Gao, YT Chua, S Deng, J Stanczyk, FZ AF Hsing, AW Gao, YT Chua, S Deng, J Stanczyk, FZ TI Insulin resistance and prostate cancer risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POPULATION; LEPTIN; CHINA; GENE AB Because high waist-to-hip ratio (WHR) and high serum insulin levels have been reported to be associated with an increased risk of prostate cancer, we assessed the relationship between insulin resistance and prostate cancer risk in Chinese men. We measured fasting serum glucose and insulin levels in 128 case and 306 control subjects and used the homeostasis model assessment to derive indices of insulin sensitivity and resistance. Relative to men in the lowest tertiles, men in the highest tertile of insulin sensitivity had a reduced risk of prostate cancer (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.21 to 0.60), but men in the highest tertile of insulin resistance had an increased risk of prostate cancer (OR = 2.78, 95% CI = 1.63 to 4.72). Considering insulin resistance and WHR together, the effect of insulin resistance was apparent in all tertiles of WHR, with men in the highest tertile of insulin resistance and WHR having the highest risk (OR = 8.21, 95% CI = 2.84 to 23.70). The associations between prostate cancer risk and insulin sensitivity or resistance were independent of total caloric intake and serum levels of insulin-like growth factors, sex hormones, and sex hormone-binding globulin. Because of the retrospective design of this study, the role of insulin resistance in prostate cancer needs to be confirmed in prospective studies. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. Columbia Univ, Dept Pediat, Div Mol Genet, New York, NY 10027 USA. Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS MSC 7234,6120 Execut Blvd, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK26687] NR 19 TC 121 Z9 124 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 1 PY 2003 VL 95 IS 1 BP 67 EP 71 PG 5 WC Oncology SC Oncology GA 629YB UT WOS:000180079200013 PM 12509402 ER PT J AU Jen, J Vogelstein, B AF Jen, J Vogelstein, B TI Tumor location and detection of K-Ras mutations in stool from colorectal cancer patients - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Ctr Canc Res, Lab Populat Genet, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. RP Jen, J (reprint author), NCI, Ctr Canc Res, Lab Populat Genet, Bldg 41,Rm D702,41 Lib Dr, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 1 PY 2003 VL 95 IS 1 BP 73 EP 73 PG 1 WC Oncology SC Oncology GA 629YB UT WOS:000180079200015 ER PT J AU Brant, LJ Sheng, SL Morrell, CH Verbeke, GN Lesaffre, E Carter, HB AF Brant, LJ Sheng, SL Morrell, CH Verbeke, GN Lesaffre, E Carter, HB TI Screening for prostate cancer by using random-effects models SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE cancer diagnosis; classification; disease screening; linear mixed effects model; longitudinal-data; prostate-specific antigen ID PROPORTIONAL HAZARDS MODEL; ANTIGEN; ERROR; SURVIVAL; TIMES; MEN; ADENOCARCINOMA; DISEASE; SERUM AB Random-effects models are used to screen male participants in a long-term longitudinal study for prostate cancer. By using posterior probabilities, each male can be classified into one of four diagnostic states for prostate disease: normal, benign prostatic hyperplasia, local cancer and metastatic cancer. Repeated measurements of prostate-specific antigen, collected when there was no clinical evidence of prostate disease, are used in the classification process. An individual's screening data are considered one repeated measurement at a time as his data are collected longitudinally over time. Posterior probabilities are calculated on the basis of data from other individuals with confirmed diagnoses of each of the four diagnostic states. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Loyola Coll, Baltimore, MD 21210 USA. Katholieke Univ Leuven, Louvain, Belgium. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Brant, LJ (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Verbeke, Geert/I-5587-2015 NR 24 TC 14 Z9 15 U1 1 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0964-1998 J9 J ROY STAT SOC A STA JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2003 VL 166 BP 51 EP 62 DI 10.1111/1467-985X.00258 PN 1 PG 12 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 641XM UT WOS:000180772400004 ER PT J AU Korn, EL Graubard, BI AF Korn, EL Graubard, BI TI Estimating variance components by using survey data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE mixed models; multilevel models; multistage sampling; random effects; sample surveys; sample weights ID SELECTION AB Inflation-type weighted estimators for variance components can be badly biased. Modified weighted estimators suggested in the literature are also badly biased for certain sampling designs. We propose new estimators for variance components, some of which are approximately unbiased regardless of the sampling design. These estimators require knowledge of the joint inclusion probabilities of the observations. The small sample properties of the estimators are studied via simulation for the simple one-way random-effects model. An application is given by using data from the US Hispanic Health and Nutrition Examination Survey. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN-8128, Bethesda, MD 20892 USA. NR 16 TC 26 Z9 26 U1 0 U2 1 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2003 VL 65 BP 175 EP 190 DI 10.1111/1467-9868.00379 PN 1 PG 16 WC Statistics & Probability SC Mathematics GA 645UB UT WOS:000180996800010 ER PT J AU Dobbin, KK Louis, TA AF Dobbin, KK Louis, TA TI Accommodating stochastic departures from percentile invariance in causal models SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE causal inference; clinical trials; permutation models; treatment adherence ID INFERENCE; RANDOMIZATION AB Consider a clinical trial in which participants are randomized to a single-dose treatment or a placebo control and assume that the adherence level is accurately recorded. If the treatment is effective, then good adherers in the treatment group should do better than poor adherers because they received more drug; the treatment group data follow a dose-response curve. But, good adherers to the placebo often do better than poor adherers, so the observed adherence-response in the treatment group cannot be completely attributed to the treatment. Efron and Feldman proposed an adjustment to the observed adherence-response in the treatment group by using the adherence-response in the control group. It relies on a percentile invariance assumption under which each participant's adherence percentile within their assigned treatment group does not depend on the assigned group (active drug or placebo). The Efron and Feldman approach is valid under percentile invariance, but not necessarily under departures from it. We propose an analysis based on a generalization of percentile invariance that allows adherence percentiles to be stochastically permuted across treatment groups, using a broad class of stochastic permutation models. We show that approximate maximum likelihood estimates of the underlying dose-response curve perform well when the stochastic permutation process is correctly specified and are quite robust to model misspecification. C1 NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Dobbin, KK (reprint author), NCI, Mailstop 7434,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2003 VL 65 BP 837 EP 849 DI 10.1111/1467-9868.00418 PN 4 PG 13 WC Statistics & Probability SC Mathematics GA 744YC UT WOS:000186659600004 ER PT J AU Cesen-Cummings, K Houston, KD Copland, JA Moorman, VJ Walker, CL Davis, BJ AF Cesen-Cummings, K Houston, KD Copland, JA Moorman, VJ Walker, CL Davis, BJ TI Uterine leiomyomas express myometrial contractile-associated proteins involved in pregnancy-related hormone signaling SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article DE uterus; myometrium; leiomyoma; parturition; oxytocin receptor ID OXYTOCIN RECEPTOR; GENE-EXPRESSION; GAP-JUNCTIONS; RAT UTERUS; ESTROUS-CYCLE; CELL-LINES; PARTURITION; PROLIFERATION; LABOR; CONNEXIN-43 AB OBJECTIVE: We used an animal model to study uterine leiomyoma in the context of pregnancy-associated changes in gene expression and to determine how they might modulate tumor growth. METHODS: Spontaneous tumors and normal myometrium were collected from Eker rats and compared with myometrial samples from pregnant animals. A leiomyoma-derived cell line was also used to assess pregnancy-related changes in gene expression and to determine the impact of signaling by the oxytocin receptor. RESULTS: Eker rat leimyomas expressed several pregnancy-related genes, including connexin 43, oxytocin receptor (OTR), and cyclooxygenase (COX)-1; however, the tumors did not express COX-2, which is expressed in the perturient, binds to oxytocin, and exhibits a calcium flux when stimulated with oxytocin. The OTR signaling mediated by oxytocin inhibited estrogen-stimulated growth of leimyoma cells. CONCLUSION: Leiomyoma cells expressed many genes of the parturient myometrium, including OTRs, but were deficient in COX-2 expression. Signaling via the OTR appears to inhibit estrogen-induced cell proliferation, suggesting that signaling by this receptor might help mediate the protective effect of pregnancy on this disease. Copyright (C) 2003 by the Society for Gynecologic Investigation. C1 Natl Inst Environm Hlth Sci, Lab Womens Hlth, Res Triangle Pk, NC USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Davis, BJ (reprint author), POB 12233,Mail Drop A2-01, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES 07784, ES 08263] NR 49 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD JAN PY 2003 VL 10 IS 1 BP 11 EP 20 AR PII S1071-5576(02)00191-0 DI 10.1016/S1071-5576(02)00191-0 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 639LA UT WOS:000180629000003 PM 12517588 ER PT J AU Aposhian, HV Morgan, DL Queen, HLS Maiorino, RM Aposhian, MM AF Aposhian, HV Morgan, DL Queen, HLS Maiorino, RM Aposhian, MM TI Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Article DE mercury vapor; vitamin C; glutathione; lipoic acid; mercury; brain mercury ID MESO-2,3-DIMERCAPTOSUCCINIC ACID; CHELATING AGENT; ASCORBIC-ACID; DIMERCAPTOSUCCINIC ACID; OCCUPATIONAL EXPOSURE; DMSA; DMPS; EXCRETION; CHLORIDE; 2,3-DIMERCAPTOPROPANE-1-SULFONATE AB Some medical practitioners prescribe GSH and vitamin C alone or in combination with DMPS or DMSA for patients with mercury exposure that is primarily due to the mercury vapor emitted by dental amalgams. Hypothesis. This study tested the hypothesis that GSH, vitamin C, or lipoic acid alone or in combination with DMPS or DMSA would decrease brain mercury. Methods. Young rats were exposed to elemental mercury by individual nose cone, at the rate of 4.0 mg mercury per m(3) air for 2 h per day for 7 consecutive days. After a 7-day equilibrium period, DMPS, DMSA, GSH, vitamin C, lipoic acid alone, or in combination was administered for 7 days and the brain and kidneys of the animals removed and analyzed for mercury by cold vapor atomic absorption. Results: None of these regimens reduced the mercury content of the brain. Although DMPS or DMSA was effective in reducing kidney mercury concentrations, GSH, vitamin C, lipoic acid alone, or in combination were not. Conclusion. One must conclude that the palliative effect, if any, of GSH, vitamin C, or lipoic acid for treatment of mercury toxicity due to mercury vapor exposure does not involve mercury mobilization from the brain and kidney. C1 Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. Inst Hlth Realities, Colorado Springs, CO USA. RP Aposhian, HV (reprint author), Univ Arizona, Dept Mol & Cellular Biol, Life Sci S Bldg,Rm 444,POB 210106, Tucson, AZ 85721 USA. NR 37 TC 18 Z9 18 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 2003 VL 41 IS 4 BP 339 EP 347 DI 10.1081/CLT-120022000 PG 9 WC Toxicology SC Toxicology GA 701AF UT WOS:000184142800002 PM 12870874 ER PT J AU Lee, W DeVore, GR Comstock, CH Kalache, KD McNie, B Chaiworapongsa, T Conoscenti, G Treadwell, MC Johnson, A Huang, RW Romero, R AF Lee, W DeVore, GR Comstock, CH Kalache, KD McNie, B Chaiworapongsa, T Conoscenti, G Treadwell, MC Johnson, A Huang, RW Romero, R TI Nasal bone evaluation in fetuses with Down Syndrome during the second and third trimesters of pregnancy SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetus; nasal bone; prenatal diagnosis; three-dimensional ultrasonography; trisomy 21 ID 2ND-TRIMESTER ULTRASOUND; AXIAL SKELETON; TRISOMY-21; MALFORMATIONS; ABSENCE; PATTERN AB Objective. This study examined the use of three-dimensional ultrasonography for evaluating the fetal nasal bone, as a sonographic marker of Down syndrome, during the second and early third trimesters of pregnancy. Methods. Forty fetuses, including 20 with trisomy 21, were scanned once by three-dimensional ultrasonography. A midline sagittal view of the facial profile was used to analyze the volume data. Independent examiners reviewed blinded and randomly allocated volume data sets for the nasal bone. Interobserver reliability was evaluated for the sonographic presence or absence of the nasal bone. Logistic regression determined the contribution of this parameter to the presence of Down syndrome. Results. Both examiners showed substantial agreement in scoring whether the nasal bone was visualized by three-dimensional ultrasonography (P <.001). They identified 40% to 45% of fetuses with abnormalities using the absence of the nasal bone as a sonographic marker. However, a substantial number of fetuses with abnormalities were also found to have a nasal bone present. The nasal bone was visualized in 80% to 90% of fetuses without abnormalities. Conclusions. Three-dimensional ultrasonography can be used to evaluate the fetal nasal bone with substantial interobserver agreement during the second and early third trimesters of pregnancy. A nonvisualized nasal bone identified 40% to 45% of fetuses with Down syndrome in this study. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. William Beaumont Hosp, Div Biostat, Royal Oak, MI 48073 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Wayne State Univ, Hutzel Hosp, Detroit, MI USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. NR 15 TC 28 Z9 30 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JAN PY 2003 VL 22 IS 1 BP 55 EP 60 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 632ZT UT WOS:000180255300009 PM 12523611 ER PT J AU Lee, W Kalache, KD Chaiworapongsa, T Londono, J Treadwell, MC Johnson, A Romero, R AF Lee, W Kalache, KD Chaiworapongsa, T Londono, J Treadwell, MC Johnson, A Romero, R TI Three-dimensional power Doppler ultrasonography during pregnancy SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetus; power Doppler ultrasonography; prenatal diagnosis; three-dimensional ultrasonography ID CYSTIC ADENOMATOID MALFORMATION; BRONCHOPULMONARY SEQUESTRATION; PRENATAL-DIAGNOSIS; ANEURYSM AB Objectives. To present the appearance of fetal and placental vascular anatomic structures by three-dimensional power Doppler ultrasonography. Methods. Three-dimensional multiplanar imaging, surface rendering, and volume rendering were combined with power Doppler ultrasonography to show the methods, imaging artifacts, and diagnostic potential of this technology during pregnancy. Results. Fetuses with normal and abnormal vascular anatomic structures were evaluated by three-dimensional power Doppler ultrasonography The combination of several imaging modalities (e.g., three-dimensional multiplanar imaging, surface rendering, and volume rendering) with power Doppler ultrasonography is shown. Conclusions. Three-dimensional power Doppler ultrasonography is an important adjunctive method that can be used to characterize normal vascular development and circulatory anomalies of the fetus. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. NR 16 TC 17 Z9 21 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JAN PY 2003 VL 22 IS 1 BP 91 EP 97 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 632ZT UT WOS:000180255300012 PM 12523614 ER PT J AU Hwang, JJ Uchio, EM Patel, SV Linehan, WM Walther, MM Pacak, K AF Hwang, JJ Uchio, EM Patel, SV Linehan, WM Walther, MM Pacak, K TI Diagnostic localization of malignant bladder pheochromocytoma using 6-[F-18]-fluorodopamine positron emission tomography SO JOURNAL OF UROLOGY LA English DT Article DE pheochromocytoma; bladder neoplasms; tomography, emission-computed C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Hwang, JJ (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2003 VL 169 IS 1 BP 274 EP 275 DI 10.1097/01.ju.0000040140.76287.b0 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 627EX UT WOS:000179921200079 PM 12478157 ER PT J AU Uchio, EM Linehan, WM Figg, WD Walther, MM AF Uchio, EM Linehan, WM Figg, WD Walther, MM TI A phase I study of intravesical suramin for the treatment of superficial transitional cell carcinoma of the bladder SO JOURNAL OF UROLOGY LA English DT Article DE bladder; bladder neoplasms; suramin; carcinoma; transitional cell ID EPIDERMAL GROWTH-FACTOR; CYTOTOXICITY INVITRO; PROSTATE-CANCER; PROLIFERATION; EXPRESSION; THERAPY; BINDING AB Purpose: Suramin is a polysulfonated naphthylurea that inhibits proliferation and DNA synthesis of transitional cell carcinoma cell lines. Its large molecular size and negative charge inhibit bladder absorption, making suramin an excellent candidate for intravesical. chemotherapy. Intravesical suramin was evaluated in a phase I study to define dose limiting toxicity and systemic absorption, determine a starting dose and regimen for phase II studies and provide a preliminary assessment of in vivo antitumor activity. Materials and Methods: Intravesical suramin treatment was administered in 9 patients with histologically identified transitional cell carcinoma (Tcis, Ta or T1) in whom at least 1 course of standard intravesical chemotherapy (bacillus Calmette-Guerin, thiotepa or mitomycin Q had failed. Suramin was administered once weekly for 6 weeks. Patients were treated in groups of 3 using a 60 cc volume and intrapatient dose escalation schedule. Suramin doses of 0.3 to 614.4 mg./ml. were administered intravesically. The last group was treated with the same weekly dose for 6 weeks. Results: The 9 patients underwent 54 treatments with suramin. Plasma suramin concentration after treatment was 1.9 to 38.0 mug./ml. and was not related to treatment dose. The dose escalation phase was limited by the solubility of suramin in solution. Complications included self-limited bladder spasms (less than 24 hours) in 4 of 54 treatments (7%) and new or worsening vesicoureteral reflux in 3 ureters (17%). Another patient who was treated after the Foley balloon was inflated in the urethra experienced bladder spasms, skin flushing and fever (39C). Mean bladder capacity before and after treatment was 600 and 540 ml., respectively. At followup 7 patients had stage Ta tumors and 2 had carcinoma in situ. Conclusions: An intravesical suramin dose of 153 mg./ml was defined as a safe treatment parameter with acceptable plasma concentrations and minimal side effects. Phase II studies are needed to assess the antitumor activity of suramin in patients with transitional cell carcinoma of the bladder. C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Uchio, EM (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 20 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2003 VL 169 IS 1 BP 357 EP 360 DI 10.1097/01.ju.0000039381.14293.52 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 627EX UT WOS:000179921200117 PM 12478189 ER PT J AU Park, JH Lee, MK Kim, HS Kim, KL Cho, EW AF Park, JH Lee, MK Kim, HS Kim, KL Cho, EW TI Targeted destruction of the polymerized human serum albumin binding site within the preS2 region of the HBV surface antigen while retaining full immunogenicity for this epitope SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatitis B virus; polymerized human serum albumin; preS2; vaccines ID HEPATITIS-B VIRUS; VACCINE; PROTEINS; RECEPTOR; PRE-S2-REGION; IMMUNIZATION; PEPTIDES AB The 55-amino acid (a.a.) preS2 region of the hepatitis B virus (HBV) envelope protein is highly immunogenic, and antibodies against this epitope confer seroprotection against HBV infections. Accordingly, various experimental and clinical studies for developing and evaluating HBV vaccines that include this particular epitope have been reported. However, a pitfall in using preS2 epitopes as part of a vaccinating antigen is that polymerized human serum albumin (pHSA), which is a normal constituent of the human serum, binds to and makes complexes with this particular region. Consequently, it is most likely that the antigen epitope is masked by serum pHSA and subsequently not detected by the immune system. To overcome these limitations, a novel single a.a substitute of the preS2 region was designed that corresponds to a tyrosine to serine exchange at position 140 of preS2. Competitive enzyme-linked immunosorbent assay showed that this substitution completely abolishes pHSA-binding activities in the mutated preS2 peptide, and CD spectra analysis revealed that this property might have been induced by slight conformational changes in its secondary structure. Nevertheless, the original B-cell epitope was still preserved in the mutated preS2 as determined by experimental immunization in mice. In this regard, the preS2(120-145/Y140S) sequence may be an HBV vaccine where epitopes, with intrinsic properties have been deleted without affecting the immunogenicity of the epitope itself. It is expected that the inclusion of this point mutated preS2 epitope will improve the efficacy of conventional preS2-containing HBV vaccines. C1 Korea Res Inst Biosci & Biotechnol, Lab Funct Proteom, Taejon 305600, South Korea. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Dept Biol Sci, Biochem Lab, Suwon, Kyunggi Do, South Korea. RP Cho, EW (reprint author), Korea Res Inst Biosci & Biotechnol, Lab Funct Proteom, POB 115, Taejon 305600, South Korea. EM ewcho@mail.kribb.re.kr RI Park, Jung Hyun /B-5712-2015 OI Park, Jung Hyun /0000-0002-9547-9055 NR 33 TC 7 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JAN PY 2003 VL 10 IS 1 BP 70 EP 79 DI 10.1046/j.1365-2893.2003.00397.x PG 10 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 639ZD UT WOS:000180659800012 PM 12558915 ER PT J AU Denicourt, C Kozak, CA Rassart, E AF Denicourt, C Kozak, CA Rassart, E TI Gris1, a new common integration site in Graffi murine leukemia virus-induced leukemias: Overexpression of a truncated cyclin D2 due to alternative splicing SO JOURNAL OF VIROLOGY LA English DT Article ID PROVIRUS INSERTIONAL MUTAGENESIS; CELL-CYCLE; RETINOBLASTOMA PROTEIN; IDENTIFICATION; EXPRESSION; CLONING; PHASE; G(1); GENE; D1 AB The Graffi murine leukemia virus is a nondefective ecotropic retrovirus that was originally reported to induce myeloid leukemia in some strains of mice (A. Graffi, Ann. N.Y. Acad. Sci. 68:540-558, 1957). Using provirus-flanking sequences as DNA probes, we identified a new common retroviral integration site called Gris1 (for Graffi integration site 1). Viral integrations in Gris1 were detected in 13% of the tumors analyzed. The Gris1 locus was mapped to the distal region of mouse chromosome 6, 85 kb upstream of the cyclin D2 gene. Such viral integration in Gris1 causes overexpression of the normal 6.5-kb major transcript of cyclin D2 but also induces the expression of a new, alternatively spliced 1.1-kb transcript from the cyclin D2 gene that encodes a truncated cyclin D2 of 17 kDa. The expression of this 1.1-kb transcript is specific to tumors in which Gris1 is rearranged but is also detected at low levels in normal tissue. C1 Univ Quebec, Dept Sci Biol, Lab Biol Mol, Montreal, PQ H3C 3P8, Canada. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Rassart, E (reprint author), Univ Quebec, Dept Sci Biol, Lab Biol Mol, CP 8888,Succ Ctr Ville, Montreal, PQ H3C 3P8, Canada. NR 44 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 37 EP 44 DI 10.1128/JVI.77.1.37-44.2003 PG 8 WC Virology SC Virology GA 626CU UT WOS:000179855400004 PM 12477808 ER PT J AU Thimme, R Wieland, S Steiger, C Ghrayeb, J Reimann, KA Purcell, RH Chisari, FV AF Thimme, R Wieland, S Steiger, C Ghrayeb, J Reimann, KA Purcell, RH Chisari, FV TI CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSGENIC MICE; LYMPHOCYTE RESPONSIVENESS; NUCLEOCAPSID ANTIGEN; IN-VIVO; RESPONSES; CHIMPANZEES; REPLICATION; EXPRESSION; HEPATOCYTE; RESOLUTION AB Although the CD4(+)- and CD8(+)-T-cell responses to the hepatitis B virus (HBV) are thought to be crucial for the control of HBV infection, the relative contribution of each T-cell subset as an effector of viral clearance is not known. To examine this question, we monitored the course of HBV infection in control, CD4-depleted, and CD8-depleted chimpanzees. Our results demonstrate that CD8(+) cells are the main effector cells responsible for viral clearance and disease pathogenesis during acute HBV infection, and they suggest that viral clearance is mediated by both noncytolytic and cytolytic effector functions of the CD8(+)-T-cell response. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol & Expt Med, Malvern, PA USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. NIH, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. RP Chisari, FV (reprint author), Scripps Res Inst, Dept Mol & Expt Med, SBR-10,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Chisari, Francis/A-3086-2008 FU NCRR NIH HHS [R24 RR016001]; NIAID NIH HHS [R01 AI020001, R01-AI20001] NR 37 TC 422 Z9 469 U1 6 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 68 EP 76 DI 10.1128/JVI.77.1.68-76.2003 PG 9 WC Virology SC Virology GA 626CU UT WOS:000179855400007 PM 12477811 ER PT J AU De Silva, FS Moss, B AF De Silva, FS Moss, B TI Vaccinia virus uracil DNA glycosylase has an essential role in DNA synthesis that is independent of its glycosylase activity: Catalytic-site, mutations reduce virulence but not virus replication in cultured cells SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; EXTRACELLULAR ENVELOPED VIRUS; VIRAL REPLICATION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; PROTEIN MIMICRY; A20R PROTEIN; POLYMERASE; ENZYME; GENE AB Previous findings that the vaccinia virus uracil DNA glycosylase is required for virus DNA replication, coupled with an inability to isolate a mutant with an active site substitution in the glycosylase gene, were surprising, as such enzymes function in DNA repair and bacterial, yeast, and mammalian null mutants are viable. To further study the role of the viral protein, we constructed recombinant vaccinia viruses with single or double mutations (D68N and H181L) in the uracil DNA glycosylase conserved catalytic site by using a complementing cell line that constitutively expresses the viral enzyme. Although these mutations abolished uracil DNA glycosylase activity, they did not prevent viral DNA replication or propagation on a variety of noncomplementing cell lines or human primary skin fibroblasts. In contrast, replication of a uracil DNA glycosylase deletion mutant occurred only in the complementing cell line. Therefore, the uracil DNA glycosylase has an essential role in DNA replication that is independent of its glycosylase activity. Nevertheless, the conservation of the catalytic site in all poxvirus orthologs suggested an important role in vivo. This idea was confirmed by the decreased virulence of catalytic-site mutants when administered by the intranasal route to mice. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 31 TC 54 Z9 56 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 159 EP 166 DI 10.1128/JVI.77.1.159-166.2003 PG 8 WC Virology SC Virology GA 626CU UT WOS:000179855400017 PM 12477821 ER PT J AU Van Rompay, KKA Greenier, JL Cole, KS Earl, P Moss, B Steckbeck, JD Pahar, B Rourke, T Montelaro, RC Canfield, DR Tarara, RP Miller, C McChesney, MB Marthas, ML AF Van Rompay, KKA Greenier, JL Cole, KS Earl, P Moss, B Steckbeck, JD Pahar, B Rourke, T Montelaro, RC Canfield, DR Tarara, RP Miller, C McChesney, MB Marthas, ML TI Immunization of newborn rhesus macaques with Simian immunodeficiency virus (SIV) vaccines prolongs survival after oral challenge with virulent SIVmac251 SO JOURNAL OF VIROLOGY LA English DT Article ID TO-CHILD TRANSMISSION; PROTECTIVE IMMUNITY; ANTIBODY-RESPONSES; RANDOMIZED TRIAL; COTE-DIVOIRE; INFECTION; HIV-1; ZIDOVUDINE; ANKARA; PREVENTION AB There is an urgent need for active immunization strategies that, if administered shortly after birth, could protect infants in developing countries from acquiring human immunodeficiency virus (HIV) infection through breast-feeding. Better knowledge of the immunogenic properties of vaccine candidates in infants and of the effect of maternal antibodies on vaccine efficacy will aid in the development of such a neonatal HIV vaccine. Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model of pediatric HIV infection with which to address these questions. Groups of infant macaques were immunized at birth and 3 weeks of age with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol, and Env (MVA-SIVgpe) or live-attenuated SIVmac1A11. One WA-SIVgpe-immunized group had maternally derived anti-SIV antibodies prior to immunization. Animals were challenged orally at 4 weeks of age with a genetically heterogeneous stock of virulent SIVmac251. Although all animals became infected, the immunized animals mounted better antiviral antibody responses, controlled virus levels more effectively, and had a longer disease-free survival than the unvaccinated infected monkeys. Maternal antibodies did not significantly reduce the efficacy of the MVA-SIVgpe vaccine. In conclusion, although the tested vaccines delayed the onset of AIDS, further studies are warranted to determine whether a vaccine that elicits stronger early, immune responses at the time of virus exposure may be able to prevent viral infection or AIDS in infants. C1 Univ Calif Davis, California Natl Primate Res Ctr, Sch Vet Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Pathol Microbiol & Immunol, Sch Vet Med, Davis, CA 95616 USA. NIH, Viral Dis Lab, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Marthas, ML (reprint author), Univ Calif Davis, California Natl Primate Res Ctr, Sch Vet Med, Davis, CA 95616 USA. OI Pahar, Bapi/0000-0003-1949-973X FU NCRR NIH HHS [P51 RR000169, RR00169]; NIAID NIH HHS [R01 AI046320, AI39109, AI47758, AI46320, R01 AI047758] NR 51 TC 69 Z9 69 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 179 EP 190 DI 10.1128/JVI.77.1.179-190.2003 PG 12 WC Virology SC Virology GA 626CU UT WOS:000179855400019 PM 12477823 ER PT J AU Bashirova, AA Wu, L Cheng, J Martin, TD Martin, MP Benveniste, RE Lifson, JD KewalRamani, VN Hughes, A Carrington, M AF Bashirova, AA Wu, L Cheng, J Martin, TD Martin, MP Benveniste, RE Lifson, JD KewalRamani, VN Hughes, A Carrington, M TI Novel member of the CD209 (DC-SIGN) gene family in primates SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; C-TYPE LECTIN; ENDOTHELIAL-CELLS; LANGERHANS CELLS; RHESUS MACAQUE; INFECTION; BINDING; TRANS; HIV; EXPRESSION AB Two CD209 family genes identified in humans, CD209 (DC-SIGN) and CD209L (DC-SIGNR/L-SIGN), encode C-type lectins that serve as adhesion receptors for ICAM-2 and ICAM-3 and participate in the transmission of human and simian immunodeficiency viruses (HIV and SIV, respectively) to target cells in vitro. Here we characterize the CD209 gene family in nonhuman primates and show that recent evolutionary alterations have occurred in this family across primate species. All of the primate species tested, specifically, Old World monkeys (OWM) and apes, have orthologues of human CD209. In contrast, CD209L is missing in OWM but present in apes. A third family member, that we have named CD209L2, was cloned from rhesus monkey cDNA and subsequently identified in OWM and apes but not in humans. Rhesus CD209L2 mRNA was prominently expressed in the liver and axillary lymph nodes, although preliminary data suggest that levels of expression may vary among individuals. Despite a high level of sequence similarity to both human and rhesus CD209, rhesus CD209L2 was substantially less effective at binding ICAM-3 and poorly transmitted HIV type 1 and SIV to target cells relative to CD209. Our data suggest that the CD209 gene family has undergone recent evolutionary processes involving duplications and deletions, the latter of which may be tolerated because of potentially redundant functional activities of the molecules encoded by these genes. C1 NCI, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, AIDS Vaccine Program, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Lab Genomic Divers, Frederick, MD 21702 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, Basic Res Lab, Frederick, MD 21702 USA. Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. RP Carrington, M (reprint author), NCI, Intramural Res Support Program, POB B, Frederick, MD 21702 USA. RI Wu, Li/E-4330-2011 OI Wu, Li/0000-0002-5468-2487 FU NCI NIH HHS [N01CO12400, N01-CO-12400]; NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168] NR 28 TC 38 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 217 EP 227 DI 10.1128/JVI.77.1.217-227.2003 PG 11 WC Virology SC Virology GA 626CU UT WOS:000179855400023 PM 12477827 ER PT J AU Skiadopoulos, MH Vogel, L Riggs, JM Surman, SR Collins, PL Murphy, BR AF Skiadopoulos, MH Vogel, L Riggs, JM Surman, SR Collins, PL Murphy, BR TI The genome length of human parainfluenza virus type 2 follows the rule of six, and recombinant viruses recovered from non-polyhexameric-length antigenomic cDNAs contain a biased distribution of correcting mutations SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; RNA-POLYMERASE; L-PROTEIN; PARAMYXOVIRUS SIMIAN-VIRUS-5; HEMAGGLUTININ-NEURAMINIDASE; ATTENUATION PHENOTYPES; CANDIDATE VACCINE; MESSENGER-RNAS; L-GENE AB Members of the Paramyxovirinae subfamily of the Paramyxoviridae family of viruses have the unusual requirement that the nucleotide length of the viral genome must be an even multiple of six in order for efficient RNA replication, and hence virus replication, to occur. Human parainfluenza virus type 2 (HPIV2) is the only member of the genus that has been reported to have a genome length that is not an even multiple of six, and it has also been recovered from a full-length antigenomic-sense cDNA that did not conform to the "rule of six." To reexamine the issue of nucleotide length in natural isolates of HPIV2, a complete consensus genomic sequence was determined for three HPIV2 strains: Greer, Vanderbilt/1994 (V94), and Vanderbilt/1998. Each of these strains was found to have a genome length of 15,654 nucleotides (nt), thus conforming in each case to the rule of six. To directly examine the requirement that the genomic length of HPIV2 be an even multiple of six, we constructed six full-length antigenomic HPIV2/V94 cDNAs that deviated from a polyhexameric length by 0 to 5 nt. Recombinant HPIV2s were readily recovered from all of the cDNAs, including those that did not conform to the rule of six. One recombinant HPIV2 isolate was completely sequenced for each of the nonpolyhexameric antigenomic cDNAs. These were found to contain small nucleotide insertions or deletions that conferred polyhexameric length to the recovered genome. Interestingly, almost all of the length corrections occurred within the hemagglutinin-neuraminidase and large polymerase genes or the intervening intergenic region and thus were proximal to the insert that caused the deviation from the rule of six. These results demonstrate, in the context of complete infectious virus, that HPIV2 has a strong and seemingly absolute requirement for a polyhexameric genome. C1 NIAID, Infect Dis Lab, Resp Viruses Sect, NIH, Bethesda, MD 20892 USA. RP Skiadopoulos, MH (reprint author), NIAID, Infect Dis Lab, Resp Viruses Sect, NIH, Bldg 50,Room 6511,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. NR 46 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 270 EP 279 DI 10.1128/JVI.77.1.270-279.2003 PG 10 WC Virology SC Virology GA 626CU UT WOS:000179855400028 PM 12477832 ER PT J AU Johnson, WE Lifson, JD Lang, SM Johnson, RP Desrosiers, RC AF Johnson, WE Lifson, JD Lang, SM Johnson, RP Desrosiers, RC TI Importance of B-Cell responses for immunological control of variant strains of simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; NEUTRALIZATION SENSITIVITY; DISEASE PROGRESSION; GENETIC RESTRICTION; CD8(+) LYMPHOCYTES; ENVELOPE PROTEIN; AIDS; MACROPHAGES; REPLICATION; VIREMIA AB The properties of three variants of cloned simian immunodeficiency virus strain 239 (SIV239) were compared. One strain (M5) lacked five sites for N-linked carbohydrate attachment in variable regions 1 and 2 (V1 and V2) of the gp120 envelope protein, one strain (DeltaV1-V2) completely lacked VI and V2 sequences, and another (316) had nine mutations in the envelope that impart high replicative capacity for tissue macrophages. All three strains were capable of significant levels of fusion independent of CD4, and all three were considerably more sensitive to antibody-mediated neutralization than the parent strain from which they were derived. Upon experimental infection of rhesus monkeys, these three variant strains replicated to viral loads at peak height around day 14 that were indistinguishable from or only slightly less than those observed in monkeys infected with the parental SIV239 strain. Viral loads at the set point 20 to 50 weeks after infection, however, were more than 400- to 10,000-fold lower with the variant strains. Depletion of B cells around the time of infection with M5 resulted in less effective immunological control and much higher viral loads at the set point in two of three monkeys. The differences between SIV239 infection, where there is not effective immunological control, and SIVM5 infection, where there is effective immunological control, cannot be easily explained by differences in the inherent replicative capacity of the viruses; rather, they are more readily explained by differences in the effectiveness of the antibody response. These results suggest that resistance of SIV239 to antibody-mediated neutralization is very important for evading effective immunological control, for allowing continuous viral replication, for maintenance of moderate-to-high viral loads at set point, and for disease progression. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program,Lab Retroviral Pathogenesis, Frederick, MD 21702 USA. RP Desrosiers, RC (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, 1 Pine Hill Dr,Box 9102, Southborough, MA 01772 USA. FU NCI NIH HHS [N01-C0-012400]; NCRR NIH HHS [P51 RR000168, K26 RR000168, R24 RR016001, R24 RR16001]; NIAID NIH HHS [P01 AI035365, U01 AI035365] NR 50 TC 44 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 375 EP 381 DI 10.1128/JVI.77.1..375-381.2003 PG 7 WC Virology SC Virology GA 626CU UT WOS:000179855400038 PM 12477842 ER PT J AU Saunier, B Triyatni, M Ulianich, L Maruvada, P Yen, P Kohn, LD AF Saunier, B Triyatni, M Ulianich, L Maruvada, P Yen, P Kohn, LD TI Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes SO JOURNAL OF VIROLOGY LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; BLOOD DENDRITIC CELLS; PERIPHERAL-BLOOD; THYROGLOBULIN INTERACTIONS; GLYCOPROTEIN COMPLEXES; RETENTION SIGNAL; LIGAND-BINDING; INSECT CELLS; HUMAN SERA; INFECTION AB We used a baculovirus-based system to prepare structural proteins of hepatitis C virus (HCV) genotype la. Binding of this preparation to cultured human hepatic cells was both dose dependent and saturable. This binding was decreased by calcium depletion and was partially prevented by ligands of the asialoglycoprotein receptor (ASGP-R), thyroglobulin, asialothyroglobulin, and antibody against a peptide in the carbohydrate recognition domain of ASGP-R but not preimmune antibody. Uptake by hepatocytes was observed with both radiolabeled and dye-labeled HCV structural proteins. With hepatocytes expressing the hH1 subunit of the ASGP-R fused to green fluorescent protein, we could show by confocal microscopy that dye stain cointernalized with the fusion protein in an area surrounding the nucleus. Internalization was more efficient with a preparation containing p7 than with one that did not. The two preparations bound to transfected 3T3-L1 cells expressing either both (hH1 and hH2) subunits of the ASGP-R (3T3-22Z cells) or both hH1 and a functionally defective variant of hH2 (3T3-24X cells) but not to parental cells. Additionally, uptake of dye-labeled preparation containing p7 was observed with 3T3-22Z cells but not with 3T3-L1 or 3T3-24X cells or with the preparation lacking p7, suggesting that p7 regulates the internalization properties of HCV structural proteins. Our observations suggest that HCV structural proteins bind to and cointernalize with the ASGP-R in cultured human hepatocytes. C1 Ohio Univ, Edison Biotechnol Inst, Konneker Res Labs, Athens, OH 45701 USA. Ohio Univ, Coll Osteopath Med, Athens, OH 45701 USA. NIDDKD, Cell Regulat Sect, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Sect, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Saunier, B (reprint author), Ohio Univ, Edison Biotechnol Inst, Konneker Res Labs, Rm 077, Athens, OH 45701 USA. NR 69 TC 88 Z9 102 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 546 EP 559 DI 10.1128/JVI.77.1.546-559.2003 PG 14 WC Virology SC Virology GA 626CU UT WOS:000179855400055 PM 12477859 ER PT J AU Leavitt, M Park, EJ Sidorov, IA Dimitrov, DS Quinnan, GV AF Leavitt, M Park, EJ Sidorov, IA Dimitrov, DS Quinnan, GV TI Concordant modulation of neutralization resistance and high infectivity of the primary human immunodeficiency virus type 1 MN strain and definition of a potential gp41 binding site in gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; SOLUBLE CD4; IMMUNOLOGICAL CHARACTERIZATION; ANTIBODIES; HIV-1; RECEPTOR; EPITOPES; COMPLEX; REGIONS; VARIANT AB Efforts to develop a vaccine against human immunodeficiency virus type 1 (HIV-1) are complicated by resistance of virus to neutralization. The neutralization resistance phenotype of HIV-1 has been linked to high infectivity. We studied the mechanisms determining this phenotype using clones of the T-cell-line-adapted (TCLA) MN strain (MN-TCLA) and the neutralization-resistant, primary MN strain (MN-P). Mutations in the amino- and carboxy-terminal halves of gp120 and the carboxy terminus of gp41 contributed to the neutralization resistance, high-infectivity phenotype but depended upon sequences in the leucine zipper (LZ) domain of gp41. Among 23 clones constructed to map the contributing mutations, there was a very strong correlation between infectivity and neutralization resistance (R-2 = 0.81; P < 0.0001). Mutations that distinguished the gp120s of MN-P and MN-TCLA clones were clustered in or near the CD4 and coreceptor binding sites and in regions distant from those binding sites. To test the hypothesis that some of these distant mutations may interact with gp41, we determined which of them contributed to high infectivity and whether those mutations modulated gp120-gp41 association in the context of MN-P LZ sequences. In one clone, six mutations in the amino terminus of gp120, at least four of which clustered closely on the inner domain, modulated infectivity. This clone had a gp120-gp41 association phenotype like MN-P: in comparison to MN-TCLA, spontaneous dissociation was low, and dissociation induced by soluble CD4 binding was high. These results identify a region of the gp120 inner domain that may be a binding site for gp41. Our studies clarify mechanisms of primary virus neutralization resistance. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NCI, Frederick Canc Res Facil, Frederick, MD USA. RP Leavitt, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. OI Sidorov, Igor/0000-0001-6519-4983 FU NIAID NIH HHS [R01 AI037438, AI 37438, R21 AI037438] NR 47 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 560 EP 570 DI 10.1128/JVI.77.1.560-570.2003 PG 11 WC Virology SC Virology GA 626CU UT WOS:000179855400056 PM 12477860 ER PT J AU Raja, A Venturi, M Kwong, P Sodroski, J AF Raja, A Venturi, M Kwong, P Sodroski, J TI CD4 binding site antibodies inhibit human immunodeficiency virus gp120 envelope glycoprotein interaction with CCR5 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; INFLUENZA-VIRUS; TYPE-1; NEUTRALIZATION; EPITOPES; RECEPTOR; HEMAGGLUTININ; ATTACHMENT; INFECTION; MECHANISM AB The human immunodeficiency virus type 1 (HIV-1) gp120 exterior glycoprotein is conformationally flexible. Upon binding the host cell receptor, CD4, gp120 assumes a conformation that is able to bind the chemokine receptors CCR5 or CXCR4, which act as coreceptors for the virus. CD4-binding-site (CD4BS) antibodies are neutralizing antibodies elicited during natural infection that are directed against gp120 epitopes that overlap the binding site for CD4. Recent studies (S. H. Xiang et al., J. Virol. 76:9888-9899, 2002) suggest that CD4BS antibodies recognize conformations of gp120 distinct from the CD4-bound conformation. This predicts that the binding of CD4BS antibodies will inhibit chemokine receptor binding. Here, we show that Fab fragments and complete immunoglobulin molecules of CD4BS antibodies inhibit CD4-independent gp120 binding to CCR5 and cell-cell fusion mediated by CD4-independent HIV-1 envelope glycoproteins. These results are consistent with a model in which the binding of CD4BS antibodies limits the ability of gp120 to assume a conformation required for coreceptor binding. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI031783, AI31783, AI41851, R01 AI041851, AI42848, R37 AI024755, R01 AI024030, AI24030, P30 AI042848, AI24755] NR 33 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 713 EP 718 DI 10.1128/JVI.77.1.713-718.2003 PG 6 WC Virology SC Virology GA 626CU UT WOS:000179855400071 PM 12477875 ER PT J AU Fu, W Hu, WS AF Fu, W Hu, WS TI Functional replacement of nucleocapsid flanking regions by heterologous counterparts with divergent primary sequences: Effects of chimeric nucleocapsid on the retroviral replication cycle SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; SPLEEN NECROSIS VIRUS; PROTEIN ZINC-FINGER; ROUS-SARCOMA VIRUS; STRAND DNA TRANSFER; STRONG-STOP DNA; IN-VITRO; GENOMIC RNA; VIRAL-RNA AB Nucleocapsid (NC) proteins in most retroviruses have a well-conserved Cys-His box(es) as well as more divergent flanking regions that are rich in basic residues. Mutations in the flanking regions can affect RNA packaging, virus assembly, and reverse transcription of the viral RNA. To gain a further understanding of the roles of NC flanking regions in the retroviral replication cycle, we generated and characterized chimeric gag-pol expression constructs derived from murine leukemia virus and spleen necrosis virus by replacing an NC flanking region from one virus with the counterpart from the other virus. We found that all four chimeras were able to generate virions, package viral RNA, and complete the viral replication cycle. Two chimeras had mild defects in virus assembly that correlated with a decrease in the isoelectric points of NCs, suggesting that the basic nature of NC is important in virus assembly. This finding indicates that, although the primary sequences of these flanking regions have little homology, the heterologous sequences are functional both as part of the Gag polyprotein and as processed NC protein. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. NR 64 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 754 EP 761 DI 10.1128/JVI.77.1.754-761.2003 PG 8 WC Virology SC Virology GA 626CU UT WOS:000179855400078 PM 12477882 ER PT J AU Yang, ZY Wyatt, LS Kong, WP Moodie, Z Moss, B Nabel, GJ AF Yang, ZY Wyatt, LS Kong, WP Moodie, Z Moss, B Nabel, GJ TI Overcoming immunity to a viral vaccine by DNA priming before vector boosting SO JOURNAL OF VIROLOGY LA English DT Article ID EBOLA-VIRUS INFECTION; RHESUS-MONKEYS; TYPE-1 VACCINE; AIDS VACCINE; IMMUNIZATION; GLYCOPROTEIN; ADENOVIRUS; SAFETY; IMMUNOGENICITY; PREVENTION AB Replication-defective adenovirus (ADV) and poxvirus vectors have shown potential as vaccines for pathogens such as Ebola or human immunodeficiency virus in nonhuman primates, but prior immunity to the viral vector in humans may limit their clinical efficacy. To overcome this limitation, the effect of prior viral exposure on immune responses to Ebola virus glycoprotein (GP), shown previously to protect against lethal hemorrhagic fever in animals, was studied. Prior exposure to ADV substantially reduced the cellular and humoral immune responses to GP expressed by ADV, while exposure to vaccinia inhibited vaccine-induced cellular but not humoral responses to GP expressed by vaccinia. This inhibition was largely overcome by priming with a DNA expression vector before boosting with the viral vector. Though heterologous viral vectors for priming and boosting can also overcome this effect, the paucity of such clinical viral vectors may limit their use. In summary, it is possible to counteract prior viral immunity by priming with a nonviral, DNA vaccine. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98109 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 30 TC 150 Z9 154 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 1 BP 799 EP 803 DI 10.1128/JVI.77.1.799-803.2003 PG 5 WC Virology SC Virology GA 626CU UT WOS:000179855400084 PM 12477888 ER PT J AU Thomson, M Nascimbeni, M Havert, MB Major, M Gonzales, S Alter, H Feinstone, SM Murthy, KK Rehermann, B Liang, TJ AF Thomson, M Nascimbeni, M Havert, MB Major, M Gonzales, S Alter, H Feinstone, SM Murthy, KK Rehermann, B Liang, TJ TI The clearance of hepatitis C virus infection in chimpanzees may not necessarily correlate with the appearance of acquired immunity SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSE; MOLECULAR CLONE; VIRAL CLEARANCE; CDNA CLONE; GENOTYPE 1B; PERSISTENCE; TRANSCRIPTS; STABILITY; RECOVERY; SEQUENCE AB Clearance of hepatitis C virus (HCV) infection in humans and chimpanzees is thought to be associated with the induction of strong T-cell responses. We studied four chimpanzees infected with HCV derived from an infectious full-length HCV genotype 1b cDNA. Two of the chimpanzees cleared the infection to undetectable levels for more than 12 months of follow-up; the other two became persistently infected. Detailed analyses of HCV-specific immune responses were performed during the courses of infection in these chimpanzees. Only weak and transient T helper responses were detected during the acute phase in all four chimpanzees. A comparison of the frequency of gamma interferon (IFN-gamma)-producing CD4(+) and CD8(+) T cells in peripheral blood by ELISpot assay did not reveal any correlation between viral clearance and T-cell responses. In addition, analyses of IFN-gamma, IFN-alpha, and interleukin-4 mRNA levels in liver biopsies, presumably indicative of intrahepatic T-cell responses, revealed no distinct pattern in these chimpanzees with respect to infection outcome. The present study suggests that the outcome of HCV infection in chimpanzees is not necessarily attributable to HCV sequence variation and that chimpanzees may recover from HCV infection by mechanisms other than the induction of readily detectable HCV-specific T-cell responses. C1 NIDDK, Liver Dis Sect, Bethesda, MD 20892 USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78227 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH Bldg 10,Rm 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HB-27091, N01HB27091] NR 31 TC 66 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 862 EP 870 DI 10.1128/JVI.77.2.862-870.2003 PG 9 WC Virology SC Virology GA 631KH UT WOS:000180166600006 PM 12502802 ER PT J AU Imamichi, T Murphy, MA Adelsberger, JW Yang, J Watkins, CM Berg, SC Baseler, MW Lempicki, RA Guo, JH Levin, JG Lane, HC AF Imamichi, T Murphy, MA Adelsberger, JW Yang, J Watkins, CM Berg, SC Baseler, MW Lempicki, RA Guo, JH Levin, JG Lane, HC TI Actinomycin D induces high-level resistance to thymidine analogs in replication of human immunodeficiency virus type 1 by interfering with host cell thymidine kinase expression SO JOURNAL OF VIROLOGY LA English DT Article ID SINGLE-STRANDED-DNA; HIV-1 REVERSE-TRANSCRIPTASE; IN-VITRO; LEUKEMIA-VIRUS; PROTEASE GENE; TAX PROTEIN; VIRAL-DNA; D-BINDING; HTLV-III; RNA AB Actinomycin D (ActD) is a transcription inhibitor and has been used in the treatment of certain forms of cancer. ActD has been reported to be a potential inhibitor of human immunodeficiency virus type I (HIV-1) replication due to its ability to inhibit reverse transcription. In contrast to what was expected, low concentrations of ActD (I to 10 nM) upregulated HIV-1 replication 8- to 10-fold in MT-2 cells and had no effect on HIV-2 replication or on HIV-1 replication in MT-4, Jurkat, or peripheral blood mononuclear cells. The upregulation of HIV-1 replication was associated with an increase in HIV-1 transcription and a decrease in CD4 and CXCR4 expression. To further evaluate the effects of ActD on emergence of drug resistance in HIV-1 replication, a series of drug resistance assays were performed. Of interest, treatment of MT-2 cells with ActD also led to a high level of resistance to thymidine analogs (>1,000-fold increase in resistance to zidovudine and >250-fold to stavudine) but not to other nucleoside reverse transcriptases (RT), nonnucleoside RT, or protease inhibitors. This resistance appeared to be due to a suppression of host cell thymidine kinase-1 (TK-1) expression. These results indicate that ActD leads to a novel form of thymidine analog resistance by suppressing host cell TK-1 expression. These results suggest that administration of combination drugs to HIV-1-infected patients may induce resistance to antiretroviral compounds via a modification of cellular factors. C1 NCI, Lab Mol Retrovirol, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, AIDS Monitoring Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. NCI, Lab Immunopathogenesis & Bioinformat, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. NCI, Clin Serv Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Imamichi, T (reprint author), NCI, Lab Mol Retrovirol, Clin Serv Program, SAIC Frederick Inc, POB B,Bldg 550,Room 126, Frederick, MD 21702 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 63 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1011 EP 1020 DI 10.1128/JVI.77.2.1011-1020.2003 PG 10 WC Virology SC Virology GA 631KH UT WOS:000180166600021 PM 12502817 ER PT J AU Ball, SC Abraha, A Collins, KR Marozsan, AJ Baird, H Quinones-Mateu, ME Penn-Nicholson, A Murray, M Richard, N Lobritz, M Zimmerman, PA Kawamura, T Blauvelt, A Arts, EJ AF Ball, SC Abraha, A Collins, KR Marozsan, AJ Baird, H Quinones-Mateu, ME Penn-Nicholson, A Murray, M Richard, N Lobritz, M Zimmerman, PA Kawamura, T Blauvelt, A Arts, EJ TI Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINE EVALUATION SITES; LANGERHANS CELL TROPISM; LONG-TERM SURVIVORS; HIV-1 INFECTION; DISEASE PROGRESSION; MOLECULAR EPIDEMIOLOGY; PHYLOGENETIC ANALYSIS; GENETIC SUBTYPES; DUAL INFECTION; CCR5 AB Continual human immunodeficiency virus type I (HIV-1) evolution and expansion within the human population have led to unequal distribution of HIV-1 group M subtypes. In particular, recent outgrowth of subtype C in southern Africa, India, and China has fueled speculation that subtype C isolates may be more fit in vivo. In this study, nine subtype B and six subtype C HIV-1 isolates were added to peripheral blood mononuclear cell cultures for a complete pairwise competition experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant. Increased fitness of subtype B over subtype C was also observed in primary CD4(+) T cells and macrophages from different human donors but not in skin-derived human Langerhans cells. Detailed analysis of the retroviral life cycle during several B and C virus competitions indicated that the efficiency of host cell entry may have a significant impact on relative fitness. Furthermore, phyletic analyses of fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate, higher fitness mapped to the subtype B env gene rather than the subtype C gag and pot genes. These results suggest that subtype B and C HIV-1 may be transmitted with equal efficiency (Langerhans cell data) but that subtype C isolates may be less fit following initial infection (T-cell and macrophage data) and may lead to slower disease progression. C1 Case Western Reserve Univ, Div Infect Dis, Dept Med, Cleveland, OH 44106 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Virol, Cleveland, OH 44195 USA. Case Western Reserve Univ, Dept Med, Div Geog Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Mol Virol Program, Cleveland, OH 44106 USA. RP Arts, EJ (reprint author), Case Western Reserve Univ, Div Infect Dis, Dept Med, BRB 1029,10900 Euclid Ave, Cleveland, OH 44106 USA. FU NHLBI NIH HHS [HL67610-02, K01 HL067610]; NIAID NIH HHS [AI36219, AI49170, P30 AI036219, R01 AI049170, R21 AI049170, R56 AI049170]; NICHD NIH HHS [N01-HD-0-3310-502-02]; NIGMS NIH HHS [T32 GM007250] NR 80 TC 141 Z9 150 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1021 EP 1038 DI 10.1128/JVI.77.2.1021-1038.2003 PG 18 WC Virology SC Virology GA 631KH UT WOS:000180166600022 PM 12502818 ER PT J AU Hanlon, L Barr, NI Blyth, K Stewart, M Haviernik, P Wolff, L Weston, K Cameron, ER Neil, JC AF Hanlon, L Barr, NI Blyth, K Stewart, M Haviernik, P Wolff, L Weston, K Cameron, ER Neil, JC TI Long-range effects of retroviral insertion on c-myb: Overexpression may be obscured by silencing during tumor growth in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; T-CELL LYMPHOMAGENESIS; PROVIRUS INTEGRATION SITE; TRANSGENIC MICE; MOUSE CHROMOSOME-10; OVER-EXPRESSION; V-MYB; GENE; PROTEINS; APOPTOSIS AB The c-myb oncogene is a frequent target for retroviral activation in hemopoietic tumors of avian and mammalian species. While insertions can target the gene directly, numerous clusters of retroviral insertion sites have been identified which map close to c-myb and outside the transcription unit in T-lymphomas (Ahi-1, fit-1, and Mis-2) and monocytic and myeloid leukemias (Mml1, Mml2, Mml3, and Epi-1). Previous analyses showed no consistent effect of these insertions on c-myb expression, raising the possibility that other nearby genes were the true targets. In contrast, our analysis of four cell lines established from lymphomas bearing insertions at fit-1 (fti-1) (feline leukemia virus) and Ahi-1 (Moloney murine leukemia virus) shows that these display higher expression levels of c-myb RNA and protein compared to a panel of phenotypically similar cell lines lacking such insertions. An interesting feature of the cell lines with long-range c-myb insertions was that each also carried an activated Myc allele. The potential for oncogenic synergy between Myb and Myc in T-cell lymphoma was confirmed in transgenic mice overexpressing alleles of both genes in the T-cell compartment, lending further credence to the case for c-myb as the major target for long-range activation. In contrast, mapping and analysis of c-myb neighboring genes (HBS1 and FLJ20069) showed that the expression of these genes did not correlate well with the presence of proviral insertions. A possible explanation for the paradoxical behavior of c-myb was provided by one of the murine T-lymphoma lines bearing an insertion at Ahi-1 (p/m16i) that reproducibly down-regulated c-myb RNA and protein to very low levels or undetectable levels on prolonged culture. Our observations implicate c-myb as a key target of upstream and downstream retroviral insertions. However, overexpression may become dispensable during outgrowth in vitro, and perhaps during tumor progression in vivo, providing a potential rationale for the previously observed discordance between retroviral insertion and c-myb expression levels. C1 Univ Glasgow, Dept Vet Pathol, Mol Oncol Lab, Glasgow G61 1QH, Lanark, Scotland. NCI, Leukemogenesis Sect, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Inst Canc Res, Ctr Cellular & Mol Biol, Canc Res UK, London SW3 6JB, England. RP Hanlon, L (reprint author), Univ Glasgow, Dept Vet Pathol, Mol Oncol Lab, Glasgow G61 1QH, Lanark, Scotland. OI Blyth, Karen/0000-0002-9304-439X NR 52 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1059 EP 1068 DI 10.1128/JVI.77.2.1059-1068.2003 PG 10 WC Virology SC Virology GA 631KH UT WOS:000180166600025 PM 12502821 ER PT J AU Kao, S Akari, H Khan, MA Dettenhofer, M Yu, XF Strebel, M AF Kao, S Akari, H Khan, MA Dettenhofer, M Yu, XF Strebel, M TI Human immunodeficiency virus type 1 Vif is efficiently packaged into virions during productive but not chronic infection SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-DEPENDENT REQUIREMENT; BLOOD MONONUCLEAR-CELLS; VIRAL-DNA SYNTHESIS; REVERSE TRANSCRIPTION; NONPERMISSIVE CELLS; RESTRICTIVE CELLS; LIFE-CYCLE; SOR GENE; PROTEIN; HIV-1 AB Packaging of the human immunodeficiency virus type I Vif protein into virus particles is mediated through an interaction with viral genomic RNA and results in the association of Vif with the nucleoprotein complex. Despite the specificity of this process, calculations of the amount of Vif packaged have produced vastly different results. Here, we compared the efficiency of packaging of Vif into virions derived from acutely and chronically infected H9 cells. We found that Vif was efficiently packaged into virions from acutely infected cells (60 to 100 copies per virion), while packaging into virions from chronically infected H9 cells was near the limit of detection (four to six copies of Vif per virion). Superinfection by an exogenous Vif-defective virus did not rescue packaging of endogenous Vif expressed in the chronically infected culture. In contrast, exogenous Vif expressed by superinfection of wild-type virus was readily packaged (30 to 40 copies per virion). Biochemical analyses suggest that the differences in the relative packaging efficiencies were not due to gross differences in the steady-state distribution of Vif in chronically or acutely infected cells but are likely due to differences in the relative rates of de novo synthesis of Vif, Despite its low packaging efficiency, endogenously expressed Vif was sufficient to direct the production of viruses with almost wild-type infectivity. The results from our study provide novel insights into the biochemical properties of Vif and offer an explanation for the reported differences regarding Vif packaging. C1 NIAID, NIH, Mol Microbiol Lab, Viral Biochem Sect, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Strebel, M (reprint author), NIAID, NIH, Mol Microbiol Lab, Viral Biochem Sect, 4-312,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. OI Dettenhofer, Markus/0000-0003-1972-7026 NR 58 TC 45 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1131 EP 1140 DI 10.1128/JVI.77.2.1131-1140.2003 PG 10 WC Virology SC Virology GA 631KH UT WOS:000180166600033 PM 12502829 ER PT J AU Skiadopoulos, MH Schmidt, AC Riggs, JM Surman, SR Elkins, WR St Claire, M Collins, PL Murphy, BR AF Skiadopoulos, MH Schmidt, AC Riggs, JM Surman, SR Elkins, WR St Claire, M Collins, PL Murphy, BR TI Determinants of the host range restriction of replication of bovine parainfluenza virus type 3 in rhesus monkeys are polygenic SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA-A VIRUS; ATTENUATION PHENOTYPES; RECEPTOR SPECIFICITY; ANTIVIRAL RESPONSES; REASSORTANT VIRUS; VACCINE; INFANTS; MUTATIONS; PRIMATES AB The Kansas strain of bovine parainfluenza virus type 3 (BPIV3) is 100- to 1,000-fold restricted in replication in the respiratory tracts of nonhuman primates compared to human PIV3 (HPIV3), an important pathogen of infants and young children. BPIV3 is also restricted in replication in human infants and children, yet it is immunogenic and is currently being evaluated in clinical trials as a vaccine candidate to protect against illness caused by HPIV3. We have examined the genetic basis for the host range attenuation phenotype of BPIV3 by exchanging each open reading frame (ORF) of a recombinant wild-type HPIV3 with the analogous ORF from BPIV3, with the caveats that the multiple ORFs of the P gene were exchanged as a single unit and that the HN and F genes were exchanged as a single unit. Recombinant chimeric bovine-human PIV3s were recovered from cDNA, and the levels of viral replication in vitro and in the respiratory tract of rhesus monkeys were determined. Recombinant chimeric HPIV3s bearing the BPIV3 N or P ORF were highly attenuated in the upper and lower respiratory tracts of monkeys, whereas those bearing the BPIV3 M or L ORF or the F and HN genes were only moderately attenuated. This indicates that the genetic determinants of the host range restriction of replication of BPIV3 for primates are polygenic, with the major determinants being the N and P ORFs. Monkeys immunized with these bovine-human chimeric viruses, including the more highly attenuated ones, developed higher levels of HPIV3 hemagglutination-inhibiting serum antibodies than did monkeys immunized with BPIV3 and were protected from challenge with wild-type HPIV3. Furthermore, host range determinants could be combined with attenuating point mutations to achieve an increased level of attenuation. Thus, chimeric recombinant bovine-human PIV3 viruses that manifest different levels of attenuation in rhesus monkeys are available for evaluation as vaccine candidates to protect infants from the severe lower respiratory tract disease caused by HPIV3. C1 NIAID, NIH, Resp Viruses Sect, Bethesda, MD 20892 USA. NIAID, NIH, Expt Primate Virol Sect, Bethesda, MD 20892 USA. NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Skiadopoulos, MH (reprint author), NIAID, NIH, Resp Viruses Sect, Bldg 50,Room 6511,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. NR 40 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1141 EP 1148 DI 10.1128/JVI.77.2.1141-1148.2003 PG 8 WC Virology SC Virology GA 631KH UT WOS:000180166600034 PM 12502830 ER PT J AU Willey, RL Byrum, R Piatak, M Kim, YB Cho, MW Rossio, JL Bess, J Igarashi, T Endo, Y Arthur, LO Lifson, JD Martin, MA AF Willey, RL Byrum, R Piatak, M Kim, YB Cho, MW Rossio, JL Bess, J Igarashi, T Endo, Y Arthur, LO Lifson, JD Martin, MA TI Control of viremia and prevention of simian-human immunodeficiency virus-induced disease in rhesus macaques immunized with recombinant vaccinia viruses plus inactivated simian immunodeficiency virus and human immunodeficiency virus type 1 particles SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; CYTOTOXIC T-LYMPHOCYTES; PBL-SCID MICE; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; HIV-1 INFECTION; IN-VIVO; PASSIVE-IMMUNIZATION; PROTECTIVE EFFICACY; VAGINAL CHALLENGE AB An effective vaccine against the human immunodeficiency virus type 1 (HIV-1) will very likely have to elicit both cellular and humoral immune responses to control HIV-1 strains of diverse geographic and genetic origins. We have utilized a pathogenic chimeric simian-human immunodeficiency virus (SHIV) rhesus macaque animal model system to evaluate the protective efficacy of a vaccine regimen that uses recombinant vaccinia viruses expressing simian immunodeficiency virus (SIV) and HIV-1 structural proteins in combination with intact inactivated SIV and HIV-1 particles. Following virus challenge, control animals experienced a rapid and complete loss of CD4(+) T cells, sustained high viral loads, and developed clinical disease by 17 to 21 weeks. Although all of the vaccinated monkeys became infected, they displayed reduced postpeak viremia, had no significant loss of CD4(+) T cells, and have remained healthy for more than 15 months postinfection. CD8(+) T-cell and neutralizing antibody responses in vaccinated animals following challenge were demonstrable. Despite the control of disease, virus was readily isolated from the circulating peripheral blood mononuclear cells of all vaccinees at 22 weeks postchallenge, indicating that immunologic control was incomplete. Virus recovered from the animal with the lowest postchallenge viremia generated high virus loads and an irreversible loss of CD4(+) T-cell loss following its inoculation into a naive animal. These results indicate that despite the protection from SHIV-induced disease, the vaccinated animals still harbored replication-competent and pathogenic virus. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Bioqual, Rockville, MD 20850 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 315,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 83 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1163 EP 1174 DI 10.1128/JVI.77.2.1163-1174.2003 PG 12 WC Virology SC Virology GA 631KH UT WOS:000180166600037 PM 12502833 ER PT J AU Xia, DX Srinivas, S Sato, H Pesnicak, L Straus, SE Cohen, JI AF Xia, DX Srinivas, S Sato, H Pesnicak, L Straus, SE Cohen, JI TI Varicella-zoster virus open reading frame 21, which is expressed during latency, is essential for virus replication but dispensable for establishment of latency SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; UL37 GENE-PRODUCT; DNA-REPLICATION; DELETION MUTANT; INFECTED-CELLS; TYPE-1 LATENCY; PROTEIN; TRANSCRIPT; IDENTIFICATION; LOCALIZATION AB Varicella-zoster virus (VZV) open reading frame 21 (ORF21) is one of at least five VZV genes expressed in latently infected human and rodent ganglia. To determine whether ORF21 is required for latent and lytic infection, we deleted 99% of ORF21 from the viral genome. The ORF21 deletion mutant virus could be propagated only in, a cell line expressing the ORF21 protein. Insertion of the herpes simplex virus type I (HSV-1) homolog of VZV ORF21, HSV-1 UL37, into the ORF21 deletion mutant failed to complement the mutant for growth in cell culture. Inoculation of cotton rats with the ORF21 deletion virus resulted in latent infection in numbers of animals similar to those infected after inoculation with the parental virus. The mean numbers of latent VZV genomes were similar in animals infected with parental and ORF21 deletion viruses. Transcription of ORF63, another latency-associated gene, was detected in ganglia from similar numbers of animals infected with the mutant and parental viruses. Thus, ORF21 is the first VZV gene expressed during latency that has been shown to be dispensable for the establishment of latent infection. C1 NIAID, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Bldg 10,Rm 11N228, Bethesda, MD 20892 USA. NR 40 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1211 EP 1218 DI 10.1128/JVI.77.2.1211-1218.2003 PG 8 WC Virology SC Virology GA 631KH UT WOS:000180166600042 PM 12502838 ER PT J AU Bonville, CA Easton, AJ Rosenberg, HF Domachowske, JB AF Bonville, CA Easton, AJ Rosenberg, HF Domachowske, JB TI Altered pathogenesis of severe pneumovirus infection in response to combined antiviral and specific immunomodulatory agents SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; COTTON RAT MODEL; AEROSOLIZED RIBAVIRIN; TRACT INFECTION; VIRAL-INFECTION; PNEUMONIA VIRUS; MESSENGER-RNA; MICE; MIP-1-ALPHA AB We report here the responses of mice with symptomatic pneumovirus infection to combined antiviral and specific immunomodulatory agents. Mice infected with pneumonia virus of mice, a natural mouse pathogen that replicates the signs and symptoms of severe infection with respiratory syncytial virus (RSV), responded to the antiviral agent ribavirin when it was administered in the setting of endogenous (gene deletion) or exogenous (antibody-mediated) blockade of the MIP-1alpha proinflammatory signaling cascade. Although neither treatment is effective alone, together they offer a dramatic reduction in symptoms and pathology, the most impressive of which is a significant reduction in morbidity and mortality. The findings presented are consistent with the notion of unique and independent contributions of virus replication and ongoing inflammation to the pathogenesis of severe respiratory virus infection, and they provide the impetus for the study of this treatment regimen in RSV-infected humans. C1 SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Upstate Med Univ, Dept Pediat, 750 E Adams St, Syracuse, NY 13210 USA. NR 34 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1237 EP 1244 DI 10.1128/JVI.77.2.1237-1244.2003 PG 8 WC Virology SC Virology GA 631KH UT WOS:000180166600045 PM 12502841 ER PT J AU Buckman, JS Bosche, WJ Gorelick, RJ AF Buckman, JS Bosche, WJ Gorelick, RJ TI Human immunodeficiency virus type 1 nucleocapsid Zn2+ fingers are required for efficient reverse transcription, initial integration processes, an protection of newly synthesized viral DNA SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; PLUS-STRAND TRANSFER; ACID-BINDING-PROTEINS; STRONG-STOP DNA; ZINC-FINGER; MINUS-STRAND; IN-VITRO; PORPHOBILINOGEN DEAMINASE; HIV-1 PARTICLES; REPLICATION AB Human immunodeficiency virus type 1 (HIV-1) containing mutations in the nucleocapsid (NC) Zn2+ finger domains have greatly reduced infectivity, even though genome packaging is largely unaffected in certain cases. To examine replication defects, viral DNA (vDNA) was isolated from cells infected with viruses containing His-to-Cys changes in their Zn2+ fingers (NCH23C and NCH44C), an integrase mutant (IND116N), a double mutant (NCH23C/IND116N), or wild-type HIV-1. In vitro assays have established potential roles for NC in reverse transcription and integration. In vivo results for these processes were obtained by quantitative PCR, cloning of PCR products, and comparison of the quantity and composition of vDNA generated at discrete points during reverse transcription. Quantitative analysis of the reverse transcription intermediates for these species strongly suggests decreased stability of the DNA produced. Both Zn2+ finger mutants appear to be defective in DNA synthesis, with the minus- and plus-strand transfer processes being affected while interior portions of the vDNA remain more intact. Sequences obtained from PCR amplification and cloning of 2-LTR circle junction fragments revealed that the NC mutants had a phenotype similar to the IN mutant; removal of the terminal CA dinucleotides necessary for integration of the vDNA is disabled by the NC mutations. Thus, the loss of infectivity in these NC mutants in vivo appears to result from defective reverse transcription and integration processes stemming from decreased protection of the full-length vDNA. Finally, these results indicate that the chaperone activity of NC extends from the management of viral RNA through to the full-length vDNA. C1 SAIC Frederick Inc, NCI, AIDS Vaccine Program, Frederick, MD 21702 USA. RP Gorelick, RJ (reprint author), SAIC Frederick Inc, NCI, AIDS Vaccine Program, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 59 TC 117 Z9 123 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1469 EP 1480 DI 10.1128/JVI.77.2.1469-1480.2003 PG 12 WC Virology SC Virology GA 631KH UT WOS:000180166600066 PM 12502862 ER PT J AU Shen, HF Suzuki, T Munroe, DJ Stewart, C Rasmussen, L Gilbert, DJ Jenkins, NA Copeland, NG AF Shen, HF Suzuki, T Munroe, DJ Stewart, C Rasmussen, L Gilbert, DJ Jenkins, NA Copeland, NG TI Common sites of retroviral integration in mouse hematopoietic tumors identified by high-throughput, single nucleotide polymorphism-based mapping and bacterial artificial chromosome hybridization SO JOURNAL OF VIROLOGY LA English DT Article ID LINKAGE MAP; LYMPHOMAS; STRAINS; GENOME; GENES; MUS AB Retroviral insertional mutagenesis in mouse hematopoietic tumors provides a powerful cancer gene discovery tool. Here, we describe a high-throughput, single nucleotide polymorphism (SNP)-based method, for mapping retroviral integration sites cloned from mouse tumors, and a bacterial artificial chromosome (BAC) hybridization method, for localizing these retroviral integration sites to common sites of retroviral integration (CISs). Several new CISs were identified, including one CIS that mapped near Notch1, a gene that has been causally associated with human T-cell tumors. This mapping method is applicable to many different species, including ones where few genetic markers and little genomic sequence information are available. It can also be used to map endogenous proviruses. C1 Natl Canc Inst Frederick, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. SAIC Frederick, Lab Mol Technol, Ft Detrick, MD 21702 USA. RP Copeland, NG (reprint author), Natl Canc Inst Frederick, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 17 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1584 EP 1588 DI 10.1128/JVI.77.2.1584-1588.2003 PG 5 WC Virology SC Virology GA 631KH UT WOS:000180166600076 PM 12502872 ER PT J AU Gao, K Gorelick, RJ Johnson, DG Bushman, F AF Gao, K Gorelick, RJ Johnson, DG Bushman, F TI Cofactors for human immunodeficiency virus type 1 cDNA integration in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-LIKE DNA; NUCLEOCAPSID PROTEIN; IN-VITRO; PREINTEGRATION COMPLEXES; CONCERTED INTEGRATION; ZINC-FINGER; EARLY STEPS; VIRAL-DNA; INVITRO; AUTOINTEGRATION AB We have investigated the function of two DNA binding proteins that stimulate human immunodeficiency virus type I cDNA integration in vitro, the cellular HMGa1 protein and the viral nucleocapsid (NC) protein. Of the three forms of NC (NCp7, NCp9, and NCp15), we find that NCp9 is the most effective at increasing integration in vitro; thus, processing of NC may potentially modulate its activities during infection. We also found that maximal stimulation by NCp9 required roughly enough NC to coat the reactant DNAs whereas less HMGa1 was required, and the reactions displayed different optima for divalent metal cofactors and order of addition. These findings reveal probable distinct mechanisms of action in vitro. C1 Salk Inst Biol Studies, Infect Dis Lab, La Jolla, CA 92037 USA. SAIC Frederick Inc, AIDS Vaccine Program, NCI, Ft Detrick, MD 21702 USA. RP Bushman, F (reprint author), Salk Inst Biol Studies, Infect Dis Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NCI NIH HHS [N01CO12400]; NIAID NIH HHS [R01 AI034786, AI34786]; NIGMS NIH HHS [GM56553] NR 35 TC 54 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1598 EP 1603 DI 10.1128/JVI.77.2.1598-1603.2003 PG 6 WC Virology SC Virology GA 631KH UT WOS:000180166600079 PM 12502875 ER PT J AU Whitehead, SS Falgout, B Hanley, KA Blaney, JE Markoff, L Murphy, BR AF Whitehead, SS Falgout, B Hanley, KA Blaney, JE Markoff, L Murphy, BR TI A live, attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide deletion in the 3 ' untranslated region is highly attenuated and immunogenic in monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID SECONDARY STRUCTURE; 3'-UNTRANSLATED REGION; CONSTRUCTION; INFECTION; SEQUENCES; STRAINS; HUMANS; FEVER AB The Delta30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN1Delta30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4Delta30 vaccine candidate. rDEN1Delta30 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN1Delta30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1Delta30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the Delta30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the Delta30 mutation into wt DEN viruses belonging to each of the four serotypes. C1 Natl Inst Allergy & Infect Dis, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA. RP Whitehead, SS (reprint author), Natl Inst Allergy & Infect Dis, Infect Dis Lab, NIH, Bldg 50mRm 6515,50 S Dr, Bethesda, MD 20892 USA. NR 22 TC 89 Z9 96 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2003 VL 77 IS 2 BP 1653 EP 1657 DI 10.1128/JVI.77.2.1653-1657.2003 PG 5 WC Virology SC Virology GA 631KH UT WOS:000180166600089 PM 12502885 ER PT J AU Stone, LS Miles, FA Banks, MS AF Stone, LS Miles, FA Banks, MS TI Linking eye movements and perception SO JOURNAL OF VISION LA English DT Editorial Material ID VISUAL-MOTION; SEARCH; SPEED C1 NASA, Human Factors Res & Technol Div, Ames Res Ctr, Moffett Field, CA 94035 USA. NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Univ Calif Berkeley, Vis Sci Program, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Stone, LS (reprint author), NASA, Human Factors Res & Technol Div, Ames Res Ctr, Moffett Field, CA 94035 USA. NR 13 TC 7 Z9 7 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2003 VL 3 IS 11 BP I EP V PG 5 WC Ophthalmology SC Ophthalmology GA 843LF UT WOS:000223082300001 ER PT J AU Sheliga, BM Miles, FA AF Sheliga, BM Miles, FA TI Perception can influence the vergence responses associated with open-loop gaze shifts in 3D SO JOURNAL OF VISION LA English DT Article DE visual perception; saccadic eye movements; vergence eye movements; induced size effect; perceived depth ID MEMORY-GUIDED SACCADES; TERM NONCONJUGATE ADAPTATION; RANDOM-DOT STEREOGRAMS; IMAGE-SIZE INEQUALITY; EYE-MOVEMENTS; ANISOMETROPIC SPECTACLES; TEMPORAL ASPECTS; VERTICAL DISPARITY; VIEWING DISTANCE; OCULAR VERGENCE AB We sought to determine if perceived depth can elicit vergence eye movements independent of binocular disparity. A flat surface in the frontal plane appears slanted about a vertical axis when the image in one eye is vertically compressed relative to the image in the other eye: the induced size effect (Ogle, 1938). We show that vergence eye movements accompany horizontal gaze shifts across such surfaces, consistent with the direction of the perceived slant, despite the absence of a horizontal disparity gradient. All images were extinguished during the gaze shifts so that eye movements were executed open-loop. We also used vertical compression of one eye's image to null the perceived slant resulting from prior horizontal compression of that image, and show that this reduces the vergence accompanying horizontal gaze shifts across the surface, even though the horizontal disparity is unchanged. When this last experiment was repeated using vertical expansions in place of the vertical compressions, the perceived slant was increased and so too was the vergence accompanying horizontal gaze shifts, although the horizontal disparity again remained unchanged. We estimate that the perceived depth accounted, on average, for 15-41% of the vergence in our experiments depending on the conditions. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Sheliga, BM (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA. FU NEI NIH HHS [Z01 EY000153-22] NR 52 TC 17 Z9 18 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2003 VL 3 IS 11 BP 654 EP 676 DI 10.1167/3.11.2 PG 23 WC Ophthalmology SC Ophthalmology GA 843LF UT WOS:000223082300003 PM 14765951 ER PT J AU Dominick, KL Skinner, CS Bastian, LA Bosworth, HB Strigo, TS Rimer, BK AF Dominick, KL Skinner, CS Bastian, LA Bosworth, HB Strigo, TS Rimer, BK TI Provider characteristics and mammography recommendation among women in their 40s and 50s SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; PRIMARY-CARE PHYSICIANS; BREAST-CANCER; SCREENING MAMMOGRAPHY; PREVENTIVE SERVICES; DECISION-MAKING; OLDER WOMEN; AGED 50; GENDER; IMPACT AB Objectives: Healthcare provider recommendation for mammography is one of the strongest predictors of women's mammography use, but few studies have examined the association of provider characteristics with mammography recommendations. We examined the relationship of provider gender, age, medical specialty, and duration of relationship with the patient to report mammography recommendation. Methods: Participants were women ages 40-45 and 50-55 who were part of a larger intervention study of decision making about mammography. We examined the relationship of provider characteristics to patient-reported mammography recommendations at baseline and at 24-month follow-up. Results: At baseline, 74% of women in their 40s and 79% of women in their 50s reported provider mammography recommendations within the prior 2 years. Proportions were similar at the 24-month follow-up. In multivariate logistic regression models including both patient and provider characteristics, women in their 40s who had female providers were more likely to report mammography recommendations than those with male providers at baseline (OR=1.83, p=0.01) and follow-up (OR=1.74, p=0.03). Among women in their 50s, participants whose regular providers were primary care physicians were more likely to report recommendations at baseline than those whose regular providers were obstetrician/gynecologists (OR=1.68, p=0.03). Conclusions: About one fourth of women in this study reported not having been advised by a healthcare provider to have a mammogram. All women in the study had health insurance. Among women in their 40s, for whom mammography guidelines were controversial at the time of data collection, provider gender was an important predictor of patient-reported mammography recommendation. C1 Durham VA Med Ctr, Durham, NC 27713 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. Duke Univ, Ctr Aging & Human Dev, Durham, NC USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Dominick, KL (reprint author), Durham VA Med Ctr, 508 Fulton St, Durham, NC 27713 USA. FU NCI NIH HHS [P01-CA-72099] NR 59 TC 14 Z9 14 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD JAN-FEB PY 2003 VL 12 IS 1 BP 61 EP 71 DI 10.1089/154099903321154158 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 651WD UT WOS:000181344400008 PM 12639370 ER PT J AU Hewitt, M Rowland, JH Yancik, R AF Hewitt, M Rowland, JH Yancik, R TI Cancer survivors in the United States: Age, health, and disability SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID QUALITY-OF-LIFE; BREAST-CANCER; PROSTATE-CANCER; CHRONIC ILLNESS; REHABILITATION; OLDER; COMORBIDITY; PREVALENCE; OUTCOMES; PATTERNS AB Background. Relatively little is known about the health and disability of adult cancer survivors. As a way to explore these issues, data from the National Health Interview Survey (years 1998-2000) were analyzed. Methods. Comparisons were made between cancer survivors (n = 4878) and those without a history of cancer (n = 90,737), using both descriptive statistics and logistic-regression models on general health status, psychological disability, limitations in activities of daily living, physical function, and health-related ability to work. Among cancer survivors, health and disability status were assessed by cancer site or type, age at diagnosis, and years since cancer diagnosis. Results. Compared with individuals without a history of cancer or other chronic disease, cancer survivors without other chronic diseases were significantly more likely to report being in fair or poor health (odds ratio, or OR, 2.97), a psychological disability (OR 2.18), limitations of activities of daily living or instrumental activities of daily living (OR 2.22), functional limitations (OR 1.74), and, among those under the age of 65, being unable to work because of a health condition (OR 3.22). The likelihood of poor health and disability was much higher among cancer survivors who also reported comorbid chronic conditions. Conclusions. Providers caring for cancer survivors should be made aware of the long-term health consequences of cancer and consider appropriate supportive care for their patients. The identification of long-term effects of cancer that contribute to disability and the interventions needed to ameliorate these and their consequences should become a more prominent aspect of the research agenda. C1 Inst Med, Natl Canc Policy Board, Washington, DC 20418 USA. NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. NIA, Geriatr & Clin Gerontol Program, NIH, Bethesda, MD 20892 USA. RP Hewitt, M (reprint author), Inst Med, Natl Canc Policy Board, 500 5th St,NAS 308, Washington, DC 20418 USA. NR 35 TC 361 Z9 367 U1 3 U2 24 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2003 VL 58 IS 1 BP 82 EP 91 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 636GB UT WOS:000180445300013 PM 12560417 ER PT J AU Petermann, AT Pippin, J Hiromura, K Monkawa, T Durvasula, R Couser, WG Kopp, J Shankland, SJ AF Petermann, AT Pippin, J Hiromura, K Monkawa, T Durvasula, R Couser, WG Kopp, J Shankland, SJ TI Mitotic cell cycle proteins increase in podocytes despite lack of proliferation SO KIDNEY INTERNATIONAL LA English DT Article DE podocyte; Cdc2; cyclin B; kidney; cell cycle; mitosis; polynucleated cells; glomerular disease ID HIV-ASSOCIATED NEPHROPATHY; MEMBRANOUS NEPHROPATHY; KINASE INHIBITORS; CDC2; GLOMERULOSCLEROSIS; PHOSPHORYLATION; B1; PATHOGENESIS; PHOSPHATASE; MATURATION AB Background. Podocyte proliferation is an uncommon response to glomerular injury and its lack may underlie the development of glomerulosclerosis. However, whether podocytes have the capacity to enter and finish mitosis and cytokinesis is not known. Methods. The expression of mitotic cell cycle proteins (phosphorylated Histone 3, Cdc2, cyclin B1 and B2) was examined by immunohistochemistry in kidneys of embryonal mice, transgenic HIV-mice, and rats with experimental membranous nephropathy (passive Heymann nephritis, PHN). Mitotic proteins also were measured by Western blot in glomerular protein from PHN-rats and the activity of mitotic cyclins was quantified by histone kinase assay. Results. Mitotic proteins were increased in embryonal mouse glomeruli during the S- and comma-shaped stages and were absent at the capillary loop stage and in mature rodent glomeruli. There was an increase in podocyte expression of Cdc2, cyclin B1 and B2 and phosphorylated histone 3 in PHN rats, and in HIV transgenic mice. Conclusions. Podocytes have the ability to increase cell cycle proteins required for mitosis. Without obvious differences in the expression of the major mitotic proteins in PHN- and HIV-nephropathy, a regulatory disturbance in cytokinesis might be responsible for the development of polynucleated cells and a lack of podocyte proliferation in experimental glomerular disease. C1 Univ Washington, Sch Med, Div Nephrol, Dept Med, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. RP Shankland, SJ (reprint author), Univ Washington, Sch Med, Div Nephrol, Dept Med, Box 356521, Seattle, WA 98195 USA. RI Monkawa, Toshiaki/F-2361-2010; OI Monkawa, Toshiaki/0000-0002-7876-7661; Kopp, Jeffrey/0000-0001-9052-186X FU NIDDK NIH HHS [DK47659, DK34198, DK52121, DK56799] NR 30 TC 40 Z9 40 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2003 VL 63 IS 1 BP 113 EP 122 DI 10.1046/j.1523-1755.2003.00723.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 624NU UT WOS:000179766600012 PM 12472774 ER PT J AU Kaysen, GA Dubin, JA Muller, HG Mitch, WE Rosales, L Levin, NW AF Kaysen, GA Dubin, JA Muller, HG Mitch, WE Rosales, L Levin, NW CA HEMO Grp TI Impact of albumin synthesis rate and the acute phase response in the dual regulation of fibrinogen levels in hemodialysis patients SO KIDNEY INTERNATIONAL LA English DT Article DE albumin synthesis; interleukin-6; plasma volume; acute phase; C-reactive protein; ceruloplasmin; alpha 1 acid glycoprotein; nutrition; body mass index; nPCR ID C-REACTIVE PROTEIN; PRO-INFLAMMATORY CYTOKINES; PLASMA-FIBRINOGEN; NEPHROTIC PATIENTS; GENE-EXPRESSION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; HEYMANN NEPHRITIS; INTERLEUKIN-6; MORTALITY AB Background. Fibrinogen is a risk factor for cardiovascular disease. It also is an acute phase protein (APP) and its plasma concentration increases with inflammation. Fibrinogen synthesis correlates with albumin synthesis in nephrotic patients and in patients with an expanded plasma volume even when serum albumin is normal and there is no inflammatory disease. The relationships among albumin synthesis, the acute phase response and plasma fibrinogen levels in hemodialysis patients are unknown. Methods. In 74 hemodialysis patients, albumin synthesis, plasma volume (PV) and acute phase proteins (APPs) C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), ceruloplasmin (Cer), and interleukin 6 (IL-6) were measured in serum and fibrinogen in plasma, and the results analyzed by multiple regression analysis. CRP, IL-6, alpha1 AG, Cer and fibrinogen were measured monthly, which enabled us to determine whether changes in these APPs correlated with the levels of and variability in plasma fibrinogen over time using a longitudinal modeling approach. Length of follow-up for the 74 patients ranged from 3.25 to 67.5 months. Results. Baseline fibrinogen (548.6 +/- 106. 4 mg/dL) was significantly greater than levels reported for normal adults and correlated positively with albumin synthesis (P < 0.001), age (P < 0.001) and log CRP (P = 0.002) and negatively with PV (P < 0.001). Longitudinally, fibrinogen varied positively with long-lived APPs, Cer and alpha1 AG, as well as the short-lived APP, CRP. Conclusion. Plasma fibrinogen concentration is high in HD patients and directly correlates with increased albumin synthesis rates and the serum levels of APPs. Fibrinogen levels also correlate negatively with PV. Fibrinogen levels vary over time in synchrony with levels of other long-lived APPs, supporting the hypothesis that fibrinogen is regulated in part as a component of the acute phase response and in part by factors that increase albumin synthesis. C1 Univ Calif Davis, Div Nephrol, Dept Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Stat, Davis, CA 95616 USA. Vet Adm No Calif Hlth Care Syst, Res Serv, Mather, CA USA. Univ Texas, Dept Med, Galveston, TX 77555 USA. Renal Res Inst, New York, NY USA. NIDDK, HEMO Study Grp, Bethesda, MD USA. Yale Univ, Div Biostat, New Haven, CT USA. RP Kaysen, GA (reprint author), Univ Calif Davis, Div Nephrol, Dept Med, TB 136, Davis, CA 95616 USA. FU NCRR NIH HHS [M01-RR00039]; NIDDK NIH HHS [R01 DK52777] NR 42 TC 25 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2003 VL 63 IS 1 BP 315 EP 322 DI 10.1046/j.1523-1755.2003.00721.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 624NU UT WOS:000179766600036 PM 12472798 ER PT J AU Allred, DC Bryant, JL Land, S Paik, S Fisher, ED Julian, T Margolese, R Smith, R Mamounas, EP Osborne, CK Fisher, B Wolmark, N AF Allred, DC Bryant, JL Land, S Paik, S Fisher, ED Julian, T Margolese, R Smith, R Mamounas, EP Osborne, CK Fisher, B Wolmark, N TI Estrogen receptor status as a predictor of the effectiveness of tamoxifen in DCIS: Findings from NSABP protocol B-24 SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Baylor Coll Med, Houston, TX 77030 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 80 BP 21A EP 21A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500095 ER PT J AU Torres-Cabala, CA Bibbo, M Roberts, DD Panizo, A Merino, MJ AF Torres-Cabala, CA Bibbo, M Roberts, DD Panizo, A Merino, MJ TI Identification of new proteins in the spectrum of thyroid lesions and their application as possible tumor markers in cytology SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 374 BP 84A EP 85A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500388 ER PT J AU Cassarino, DS Auerbach, A Miller, W Sherry, R Duray, PH AF Cassarino, DS Auerbach, A Miller, W Sherry, R Duray, PH TI The effects or gp-100 and tyrosinase vaccination on nevi in melanoma patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 393 BP 89A EP 89A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500407 ER PT J AU Auerbach, A Ronschetti, R Linehan, WM Merino, MJ AF Auerbach, A Ronschetti, R Linehan, WM Merino, MJ TI Chromogenic in situ hybridization (CISH) of chromosome 7 supports lack of association between colonic lesions and the Birt-Hogg-Dubey syndrome SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 509 BP 113A EP 113A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500522 ER PT J AU Chian-Garcia, CA Torres-Cabala, CA Eyler, R Linehan, WM Merino, MJ AF Chian-Garcia, CA Torres-Cabala, CA Eyler, R Linehan, WM Merino, MJ TI Renal cell carcinoma in children and young adults: A clinicopathological and immunohistochemical study of 14 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 659 BP 145A EP 146A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500672 ER PT J AU Datta, MW Becich, MJ Bosland, MC Dhir, R Kajdacsy-Balla, A Melamed, J Orenstein, J Silveer, S Berman, J AF Datta, MW Becich, MJ Bosland, MC Dhir, R Kajdacsy-Balla, A Melamed, J Orenstein, J Silveer, S Berman, J TI Ethnicity based analysis of prostatectomy specimens and PSA outcomes: Results of the NCI cooperative prostate cancer tissue resource SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Coll Med, Milwaukee, WI USA. Univ Pittsburgh, Pittsburgh, PA USA. NYU, Sch Med, New York, NY USA. George Washington Univ, Sch Med, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 665 BP 147A EP 147A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500678 ER PT J AU Melarned, J Datta, MW Becich, MJ Bosland, M Dhir, R Kajdacsy-Balla, A Orenstein, J Silver, S Berman, JJ AF Melarned, J Datta, MW Becich, MJ Bosland, M Dhir, R Kajdacsy-Balla, A Orenstein, J Silver, S Berman, JJ TI Prostate cancer pathologic parameters and clinical outcome: Results from the cooperative prostate cancer tissue resource (CPCTR) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NYU, Sch Med, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. George Washington Univ, Washington, DC 20052 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 737 BP 162A EP 162A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500750 ER PT J AU Merino, MJ Torres-Cabala, CA Zbar, B Chian-Garcia, CA Linehan, WM AF Merino, MJ Torres-Cabala, CA Zbar, B Chian-Garcia, CA Linehan, WM TI Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC): Clinical, histopathological and molecular features of the first american families described SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 739 BP 162A EP 162A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500752 ER PT J AU Ronchetti, RD Torres-Cabala, CA Chian-Garcia, CA Eyler, R Linehan, WM Merino, MJ AF Ronchetti, RD Torres-Cabala, CA Chian-Garcia, CA Eyler, R Linehan, WM Merino, MJ TI Detection of chromosome 7 and 17 aneuploidy in type 1 papillary renal cell carcinoma by chromogenic in situ hybridization (CISH). A comparison with other renal cell tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 761 BP 167A EP 167A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500774 ER PT J AU Ronchetti, RD Torres-Cabala, CA Chian-Garcia, CA Duray, PH Phillips, J Linehan, WM AF Ronchetti, RD Torres-Cabala, CA Chian-Garcia, CA Duray, PH Phillips, J Linehan, WM TI Expression of estrogen receptor alpha and beta, androgen receptor, and glutathione-s-transferase pi in prostatic adenocarcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 760 BP 167A EP 167A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500773 ER PT J AU Torres-Cabala, CA Worrell, RA Chian-Garcia, CA Martinez, A Merino, MJ Linehan, WM AF Torres-Cabala, CA Worrell, RA Chian-Garcia, CA Martinez, A Merino, MJ Linehan, WM TI Innumohistochemical expression of hypoxia-induced mediators and correlation with VHL gene mutation in sporadic clear cell renal cell carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 789 BP 173A EP 173A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732500802 ER PT J AU Rimsza, LM LeBlanc, M Braziel, R Jaramillo, M Miller, TP Staudt, L Grogan, TM Fisher, R AF Rimsza, LM LeBlanc, M Braziel, R Jaramillo, M Miller, TP Staudt, L Grogan, TM Fisher, R TI Loss of major histocompatibility complex (MHC) class II gene expression predicts poor survival in diffuse large B celllymphoma (DLBCL) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Univ Arizona, Tucson, AZ 85721 USA. SW Oncol Grp, Seattle, WA USA. Oregon Hlth Sci Univ, Portland, OR USA. NIH, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY 14627 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1141 BP 250A EP 250A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501154 ER PT J AU Toro, JR Liewehr, DJ Pabby, N Sorbara, L Raffeld, M Steinberg, S Jaffe, ES AF Toro, JR Liewehr, DJ Pabby, N Sorbara, L Raffeld, M Steinberg, S Jaffe, ES TI Gamma delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1167 BP 256A EP 256A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501180 ER PT J AU Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES AF Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES TI Investigation of pro-survival pathways by reverse phase protein microarray in follicular lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1190 BP 261A EP 261A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501203 ER PT J AU Quezado, MM Ronchetti, RD Harris, C Perez, JL Tavora, F Patrocinio, R Ghatak, N AF Quezado, MM Ronchetti, RD Harris, C Perez, JL Tavora, F Patrocinio, R Ghatak, N TI Correlation of EGFR gene amplification and overexpression by chromogenic in situ hybridization (CISH), and immunohistochemistry in high grade gliomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1334 BP 292A EP 292A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501347 ER PT J AU Quezado, MM Perez, JL Ronchetti, RD Ghatak, NR AF Quezado, MM Perez, JL Ronchetti, RD Ghatak, NR TI Gain of chromosome 7 in ependymomas and medulloblastomas detected by chromogenic in situ hybridization (CISH) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Virginia Commonwealth Univ, Richmond, VA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1333 BP 292A EP 292A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501346 ER PT J AU Quezado, MM Santi, M Patrocinio, RV Romero, ME Perez, JL Tsokos, M Ghatak, NR AF Quezado, MM Santi, M Patrocinio, RV Romero, ME Perez, JL Tsokos, M Ghatak, NR TI Ependymomas express death receptor 4 and death receptor 5 by immunohistochemistry SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC 20010 USA. BIOPSE Labs, Fortaleza, Ceara, Brazil. Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1335 BP 293A EP 293A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501348 ER PT J AU Fetsch, PA Abati, A Morisaki, K Honjo, Y Mittal, K Hewitt, S Bates, SE AF Fetsch, PA Abati, A Morisaki, K Honjo, Y Mittal, K Hewitt, S Bates, SE TI Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD USA. NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1348 BP 295A EP 295A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501361 ER PT J AU Debelenko, LV Romero, M Tsokos, M AF Debelenko, LV Romero, M Tsokos, M TI Expression of anaplastic lymphoma kinase (ALK) protein in pediatric tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1374 BP 301A EP 301A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501387 ER PT J AU Fukuoka, J Fujii, T Dracheva, T Travis, WD Jen, J AF Fukuoka, J Fujii, T Dracheva, T Travis, WD Jen, J TI Association of PGP9.5 staining with cyclin E, Cdk2, historic remodeling proteins in non-small cell lung cancer: Tissue microarray assessment SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1401 BP 306A EP 307A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501414 ER PT J AU Minato, H Fujii, T Hayden, D Franks, T Falk, R Travis, WD AF Minato, H Fujii, T Hayden, D Franks, T Falk, R Travis, WD TI Localized fibrous tumors (LFT) of the pleura: A clinicopathologic study or 217 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1422 BP 311A EP 311A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501435 ER PT J AU Naizhen, X Witschi, H Linnoila, I AF Naizhen, X Witschi, H Linnoila, I TI Co-expression of achaete-scute homolog-1 (ASH1) with calcitonin-gene related peptide (CGRP) and epithelial cell markers during NNK-induced pulmonary carcinogenesis in hamsters SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, NIH, Rockville, MD USA. Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1424 BP 311A EP 312A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501437 ER PT J AU Gold, R Dalakas, MC Toyka, KV AF Gold, R Dalakas, MC Toyka, KV TI Immunotherapy in autoimmune neuromuscular disorders SO LANCET NEUROLOGY LA English DT Review ID GUILLAIN-BARRE-SYNDROME; INFLAMMATORY DEMYELINATING POLYNEUROPATHY; DOSE INTRAVENOUS IMMUNOGLOBULIN; T-CELL APOPTOSIS; INHERITED PERIPHERAL NEUROPATHIES; COSTIMULATORY MOLECULE BB-1; LAMBERT-EATON SYNDROME; MYASTHENIA-GRAVIS; PLASMA-EXCHANGE; ACETYLCHOLINE-RECEPTOR AB Important progress has been made in our understanding of the cellular and molecular processes underlying autoimmune neuromuscular diseases that has led us to identify targets for rational therapeutic intervention. Although antigen-specific immunotherapy is not yet available, old and new immunomodulatory treatments, alone or in combination, provide effective immunotherapy for most autoimmune disorders. In parallel, the achievements of molecular medicine provide more specific yet largely experimental therapeutic tools that need to be tested in the human diseases. Here we review the principles and targets of immunotherapy for autoimmune neuromuscular disorders, address applications and practical guidelines, and give an outlook on future developments. C1 Univ Wurzburg, Dept Neurol, Clin Res Grp Multiple Sclerosis & Neuroimmunol, D-97080 Wurzburg, Germany. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Gold, R (reprint author), Univ Wurzburg, Dept Neurol, Clin Res Grp Multiple Sclerosis & Neuroimmunol, D-97080 Wurzburg, Germany. NR 135 TC 35 Z9 35 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2003 VL 2 IS 1 BP 22 EP 32 DI 10.1016/S1474-4422(03)00264-3 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 629DU UT WOS:000180035800020 PM 12849298 ER PT S AU Hattery, D Hattery, B Hassan, M Chernomordik, V Vogel, A Hekmat, F Gandjbakhche, A AF Hattery, D Hattery, B Hassan, M Chernomordik, V Vogel, A Hekmat, F Gandjbakhche, A BE Rechmann, P Fried, D Hennig, T TI Optical quantification of epithelial layer thickness as a measure of oral inflammation SO LASERS IN DENTISTRY IX SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Lasers in Dentistry IX CY JAN 26-27, 2003 CL SAN JOSE, CA SP SPIE DE oral; cancer; spectroscopy; inflammation; diffuse-reflectance; chemoprevention ID PHOTON MIGRATION; DIFFUSION; TISSUE; MEDIA AB For individuals with cancer risk factors, reducing tissue inflammation may reduce the risk of developing cancer. This is the basis of several clinical trials evaluating potential chemoprevention drugs. These trials require quantitative assessments of inflammation which, for the oral epithelium, are traditionally provided by punch biopsies. To reduce patient discomfort and morbidity, we have developed a non-invasive alternative using diffuse reflectance spectroscopy. Though any optical system has the potential for probing near-surface structures, traditional methods of accounting for scattering of photons are generally invalid for typical epithelial thicknesses. We have previously developed a theory that is valid in this regime and validated it with Monte Carlo simulations. We use a differential measure with acute sensitivity to small changes in layer scattering coefficients. To assess the capability of the approach to quantify epithelial thickness, detailed Monte Carlo simulations and measurements on phantom models of a two layered structure have been performed. Preliminary results from this work show that our key feature varies less than 20 percent despite four-fold changes in scattering coefficients and tenfold changes in absorption coefficients. This indicates that the method will be of practical clinical value for quantifying epithelial thickness in vivo. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Hattery, D (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4750-1 J9 P SOC PHOTO-OPT INS PY 2003 VL 4950 BP 1 EP 10 DI 10.1117/12.476656 PG 10 WC Dentistry, Oral Surgery & Medicine; Optics; Physics, Applied SC Dentistry, Oral Surgery & Medicine; Optics; Physics GA BX17C UT WOS:000184498200001 ER PT J AU Chowdhury, B Adak, M Bose, SK AF Chowdhury, B Adak, M Bose, SK TI Flurbiprofen, a unique non-steroidal anti-inflammatory drug with antimicrobial activity against Trichophyton, Microsporum and Epidermophyton species SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article DE antifungal activity; Candida albicans; dermatophytes; flurbiprofen; minimum inhibitory concentration ID ANTIBACTERIAL ACTIVITY; MYCOBACILLIN; IBUPROFEN; COMPOUND; BACTERIA AB Aims: The objective of this study was to determine the antifungal activity of flurbiprofen against dermatophytes like Trichophyton, Microsporum and Epidermophyton species. Methods and Results: Susceptibility tests were performed against dermatophytes like Trichophyton , Microsporum and Epidermophyton species by the microbroth dilution method. Among the dermatophytes tested, Trichophyton , Microsporum and Epidermophyton species are remarkably susceptible to this compound (MIC50: 8-16 mug ml(-1)). A yeast pathogen, Candida albicans, and a bacterium, Staphylococcus aureus, are also susceptible to flurbiprofen. Conclusions: Flurbiprofen is a non-steroidal anti-inflammatory compound with strong antifungal activity, which is not found in two well known and medically used antifungal organic acids like benzoic and salicylic acids. Significance and Impact of the Study: The present action of flurbiprofen on microbes indicates its future prospects as an antimicrobial agent against dermatophytes and yeast pathogens. However, in view of the anti-inflammatory property of flurbiprofen, its antifungal action may provide an additional advantage for use as a skin ointment. C1 Mem Univ Newfoundland, Dept Biol, St John, NF A1B 3X9, Canada. Jadavpur Univ, Dept Pharmaceut Technol, Kolkata 700032, W Bengal, India. Univ Calcutta, Univ Coll Sci, Dept Biochem, Kolkata 700019, W Bengal, India. RP Chowdhury, B (reprint author), NICHD, HDB, NIH, Bldg 10,Rm 9S 241, Bethesda, MD 20892 USA. EM chowdhur@mail.nih.gov NR 16 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0266-8254 EI 1472-765X J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PY 2003 VL 37 IS 2 BP 158 EP 161 DI 10.1046/j.1472-765X.2003.01370.x PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 700JH UT WOS:000184108500013 PM 12859660 ER PT J AU Yang, D Chen, Q Oppenheim, JJ Kuusela, R Taylor, JW Wade, D AF Yang, D Chen, Q Oppenheim, JJ Kuusela, R Taylor, JW Wade, D TI Temporin/VesCP (T/V)-like antibiotic peptides, derived from frogs and wasps, induce migration of human monocytos and neutrophils SO LETTERS IN PEPTIDE SCIENCE LA English DT Article DE chemotaxis; consensus sequence; D-amino acid; frog; monocyte; MRSA; neutrophil; temporin; VRE; wasp ID CECROPIN-A-TEMPORIN; ANTIMICROBIAL PEPTIDES; SKIN SECRETIONS; CHEMOTACTIC PEPTIDE; GRAFT INFECTION; EUROPEAN HORNET; HYBRID PEPTIDE; VESPA-CRABRO; LYS7 ANALOG; BROWN FROG AB Several naturally occurring antimicrobial peptides, from mammals and insects, have previously been shown to be chemotactic for human inflammatory cells. Based on this evidence, ten synthetic analogs of naturally occurring antibiotic peptides from the skin secretions of three species of Ranid frogs and the venom of one species of Vespid wasp (i.e., T/V-like peptides) were tested for their abilities to induce migration of human neutrophils and monocytes. These included temporin A (TA from Rana temporaria), temporin 1P (T1P from R. pipens), ranateurin 6 (Rana-6 from R. catesbeiana)], three TA analogs [all D-amino acids (D-TA), reversed sequence (Rev-TA), and Pro3-->Gly (G3-TA)], two frog skin-related T/V-like peptide consensus sequences (I4S10-Con and I4G10-Con), VesCP-M (VCP-M from Vespa mandarinia), and a hybrid peptide composed of portions of the insect antibiotic peptide, cecropin A (CA), and TA (CATA). TA, TIP, Rana-6, VCP-M, G3-TA, I4S10-Con, I4G10-Con, and CATA all induced cell migration at micromolar concentrations. D-TA and Rev-TA did not induce cell migration, suggesting that this process involves a chiral interaction, such as receptor binding, and also depends on the order of amino acids within TA. The results demonstrate, for the first time, that certain T/V-Iike antibiotic peptides are capable of inducing chemotaxis of human phagocytes and suggest that these peptides are multifunctional molecules with antimicrobial, hemolytic, and chernotactic capabilities. C1 Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. Wade Res Fdn, Somerset, NJ USA. SAIC, Basic Res Program, Frederick, MD USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, NIH, Frederick, MD USA. Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, Helsinki, Finland. Univ Cent Hosp, HUCH Lab Diagnost, Clin Microbiol Sect, Helsinki, Finland. RP Wade, D (reprint author), Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. EM amidebond@hotmail.com NR 58 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5666 J9 LETT PEPT SCI JI Lett. Pept. Sci. PY 2003 VL 10 IS 2 BP 99 EP 110 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867IT UT WOS:000224837000006 ER PT J AU Sei, S AF Sei, S TI Peptide nucleic acids as epigenetic inhibitors of HIV-1 SO LETTERS IN PEPTIDE SCIENCE LA English DT Review DE HIV/AIDS; peptide nucleic acids; HIV gene target ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL LEUKEMIA-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; ACUTE PROMYELOCYTIC LEUKEMIA; CHRONICALLY INFECTED-CELLS; DEFICIENCY SYNDROME AIDS; BLOOD-BRAIN-BARRIER; POL-GENE-PRODUCTS; IN-VIVO; TYPE-1 REPLICATION AB The advent of highly active antiretroviral therapy (HAART) was once perceived to have transformed deadly HIV/AIDS into a treatable, chronic infectious disease. However. mounting evidence now suggests that the prevalence of multi-drug resistant HIV (MDR-HIV) infection is steadily rising among newly infected individuals in the HAART-experienced countries, raising a concern for a future outbreak of MDR-HIV/AIDS. Our global fight against AIDS must include sustained effort to search and discover a new therapeutic modality for HIV infection. Of plausible viral targets explored to date, HIV gene-targeting approach has not yet seen a considerable success in vivo. The pursuit of anti-HIV gene intervention should include the identification of critical gene targets as well as the optimization of biomolecules that can effectively interact with the intended targets. Using unmodified peptide nucleic acids (PNA) as a biomolecular tool, we discovered a potentially critical HIV gene segment within gag-pol encoding gene. Antisense PNA targeting this specific region effectively disrupted a translation of HIV gag-pol mRNA, abolishing the virion production from chronically HIV-infected cells. This exemplifies the possibility that epigenic HIV inhibitors may be developed in the coming years, if emerging novel technologies permit sufficient and stable in vivo delivery of PNA or other similarly effective biomolecules. RP Sei, S (reprint author), NCI, SAIC, Dev Therapeut Program, Screening Technol Branch,Lab Antiviral Drug Mecha, Bldg 439, Frederick, MD 21702 USA. EM sei@dtpax2.izcifcrf.gov NR 173 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5666 J9 LETT PEPT SCI JI Lett. Pept. Sci. PY 2003 VL 10 IS 3-4 BP 269 EP 286 DI 10.1007/BF02484563 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 893PH UT WOS:000226731200010 ER PT J AU Azorsa, DO Mousses, S Caplen, NJ AF Azorsa, DO Mousses, S Caplen, NJ TI Gene silencing through RNA interference: Potential for therapeutics and functional genomics SO LETTERS IN PEPTIDE SCIENCE LA English DT Review DE functional genomics; gene therapy; RNAi; RNA interference; RNA silencing; siRNA; short interfering RNA ID DOUBLE-STRANDED-RNA; CULTURED-MAMMALIAN-CELLS; GERM-LINE DEVELOPMENT; SHORT HAIRPIN RNAS; VECTOR-BASED RNAI; C-ELEGANS; CAENORHABDITIS-ELEGANS; HIV-1 INFECTION; PROTEIN-KINASE; MESSENGER-RNA AB A major focus of biology is determining the role that specific genes play within a cell. The ability to control gene expression is a powerful tool for biologists, and methods that facilitate the expression of genes in trans have been very useful in delineating gene function. However, methods that enable researchers to decrease or inhibit gene expression in a controlled and specific manner have been lacking. A significant advancement in the field of gene silencing is the recent discovery of RNA interference (RNAi), a post-transcriptional gene silencing mechanism first described in C. elegans and Drosophila and more recently shown to occur in mammals, including mouse and human cells. This chapter will examine several aspects of RNAi and its related gene silencing, mechanisms and will discuss the impact that technologies based on these endogenous cellular processes have had on studies of gene function and on new approaches to the treatment of disease. C1 Translat Genom Res Inst, TGen, Gaithersburg, MD 20878 USA. NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. RP Caplen, NJ (reprint author), NCI, NIH, Gene Silencing Sect, Canc Res Ctr,NIH, Bldg 37,Room 3128B,37 Convent Dr, Bethesda, MD 20892 USA. EM ncaplen@mail.nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 NR 174 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5666 J9 LETT PEPT SCI JI Lett. Pept. Sci. PY 2003 VL 10 IS 3-4 BP 361 EP 372 DI 10.1007/BF02484571 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 893PH UT WOS:000226731200018 ER PT J AU Ramage, JG Vallera, DA Black, JH Aplan, PD Kees, UR Frankel, AE AF Ramage, JG Vallera, DA Black, JH Aplan, PD Kees, UR Frankel, AE TI The diphtheria toxin/urokinase fusion protein (DTAT) is selectively toxic to CD87 expressing leukemic cells SO LEUKEMIA RESEARCH LA English DT Article DE acute myeloid leukemia; diphtheria fusion protein; urokmase receptor ID PLASMINOGEN-ACTIVATOR RECEPTOR; PERIPHERAL-BLOOD CELLS; ACUTE MYELOID-LEUKEMIA; UROKINASE-RECEPTOR; MOLECULAR ANALYSIS; ENDOTHELIAL-CELLS; OLDER PATIENTS; LINE; BINDING; TRANSLOCATION AB Diphtheria fusion proteins are a novel class of agents for the treatment of chemotherapy resistant acute myelogenous leukemia (AML). We prepared diphtheria toxin/urokinase fusion protein (DTAT) composed of the amino terminal fragment of the urokinase-type plasminogen activator (uPA) fused to the catalytic and translocation domains of diphtheria toxin (DT) and assessed its activity on leukemic cell lines. The number of uPA receptors (uPAR or CD87) was measured using a phycoerythrin conjugated monoclonal antibody to CD87 and flow cytometry. Seven of 23 cell lines (30%) showed CD87 expression (greater than or equal to5000 receptors/cell). DTAT cytotoxicity (IC50 less than or equal to 30 pM) was observed in all seven of these samples and none of the 16 samples with low or absent CD87 expression. There was a significant correlation between DTAT sensitivity and CD87 density (P = 0.0007). These results show that specific CD87 binding is one factor important in the sensitivity of patient's leukemic blasts to DTAT and demonstrate for the first time that the CD87/uPAR can be used as a target for fusion protein therapy of AML. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. Univ Minnesota, Ctr Canc, Dept Therapeut Radiol & Radiat Oncol, Minneapolis, MN USA. NCI, Dept Genet, Bethesda, MD 20892 USA. Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Perth, WA 6009, Australia. RP Frankel, AE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA. RI Aplan, Peter/K-9064-2016 FU NCI NIH HHS [R01CA090,263, R01CA76,178, R21CA90,550] NR 51 TC 23 Z9 24 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2003 VL 27 IS 1 BP 79 EP 84 AR PII S0145-2126(02)00077-2 DI 10.1016/S0145-2126(02)00077-2 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 638JW UT WOS:000180568700012 PM 12479856 ER PT J AU Hofmann, A Huber, R AF Hofmann, A Huber, R TI Liposomes in assessment of annexin-membrane interactions SO LIPOSOMES, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID LARGE UNILAMELLAR VESICLES; PROTEIN-KINASE-C; CA-2+-DEPENDENT PHOSPHOLIPID-BINDING; TIME-RESOLVED FLUORESCENCE; CALCIUM-DEPENDENT BINDING; ION INDUCED FUSION; AGGREGATION; MECHANISM; BILAYERS; PHOSPHORYLATION C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RP Hofmann, A (reprint author), NCI, Macromol Crystallog Lab, 539 Boyles St, Frederick, MD 21702 USA. RI Hofmann, Andreas/B-9515-2008 OI Hofmann, Andreas/0000-0003-4408-5467 NR 86 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 372 BP 186 EP 216 PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX89B UT WOS:000186734500011 PM 14610814 ER PT J AU Bhargava, R Wang, SQ Koenig, JL AF Bhargava, R Wang, SQ Koenig, JL TI FTIR microspectroscopy of polymeric systems SO LIQUID CHROMATOGRAPHY FTIR MICROSPECTROSCOPY MICROWAVE ASSISTED SYNTHESIS SE ADVANCES IN POLYMER SCIENCE LA English DT Review ID TRANSFORM INFRARED MICROSPECTROSCOPY; DISPERSED LIQUID-CRYSTALS; FIBER-REINFORCED COMPOSITES; PLANE ARRAY DETECTION; IN-SITU DIFFUSION; IR MICROSPECTROSCOPY; ORIENTATION DISTRIBUTION; CONCENTRATION PROFILES; SPATIAL-RESOLUTION; PDLC SYSTEMS AB Fourier transform infrared (FTIR) spectroscopy is a mature analytical technique employed to examine polymeric materials. With the coupling of an infrared interferometer to a microscope equipped with specialized detectors, FTIR spectroscopy has been employed widely to examine microscopic areas in polymers for the last twenty years. Following the emergence of instrumentation techniques that employ focal plane array (FPA) detectors, FTIR microspectroscopy has experienced a recent renaissance in terms of the capability of instrumentation and visualization afforded for examining multicomponent polymer systems. We present an overview of the principles of instrumental configurations used to achieve spatially resolved spectral information, their relative advantages and limitations. Illustrative examples are presented that demonstrate the capabilities of FTIR microspectroscopy and the insight this technique provides into the composition, formation, and behavior of polymeric materials. Finally, some emerging techniques that may permit microspectroscopic analyses on a different spatial scale are reviewed. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Akron, Dept Polymer Sci, Akron, OH 44325 USA. Case Western Reserve Univ, Dept Macromol Sci, Cleveland, OH 44106 USA. RP Bhargava, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Wang, Shi-Qing/A-1399-2009; Suter, Ulrich/H-8900-2013; OI Suter, Ulrich/0000-0001-7467-7346; Bhargava, Rohit/0000-0001-7360-994X NR 144 TC 56 Z9 56 U1 8 U2 37 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-3195 J9 ADV POLYM SCI PY 2003 VL 163 BP 137 EP 191 DI 10.1007/b11052 PG 55 WC Polymer Science SC Polymer Science GA BX77C UT WOS:000186351000003 ER PT J AU Sundaramurthy, S Bush, TM Neuwelt, C Ward, MM AF Sundaramurthy, S Bush, TM Neuwelt, C Ward, MM TI Time perspective predicts the progression of permanent organ damage in patients with systemic lupus erythematosus SO LUPUS LA English DT Article DE organ damage; socioeconomic status; systemic lupus erythematosus; time perspective ID LONGITUDINAL DATA-ANALYSIS; SOCIOECONOMIC-STATUS; DISEASE-ACTIVITY; HEALTH; OUTCOMES; FUTURE; INDEX; DURATION; RACE; PREFERENCES AB Patients whose perspective is oriented to the future more than to the present may have better long-term health outcomes. We examined if time perspective predicted future organ damage in patients with systemic lupus erythematosus (SLE). We assessed the time perspectives of 87 patients with SLE using a questionnaire at a baseline visit. Permanent organ damage was assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index during the same visit, and reassessed after a median of 4.6 years. Patients who were oriented more to the future were less likely to have an increase in the Damage Index than those oriented more to the present. In a multivariate analysis, each 1-point increase in the degree of orientation to the future (on a scale of 1-6) was associated with a 22% decrease in the likelihood that the Damage Index would increase over time (odds ratio 0.78; 95% confidence interval 0.64-0.94; P = 0.009). Other measures that predicted an increase in the Damage Index were lower education levels, greater health locus of control attributed to chance and greater health locus of control attributed to powerful others. In conclusion, time perspective is a significant predictor of future organ damage in SLE. Patients who have a greater orientation to the future are less likely to develop permanent organ damage. C1 Stanford Univ, Sch Med, Div Rheumatol & Immunol, Dept Med, Stanford, CA 94305 USA. Santa Clara Valley Med Ctr, Dept Med, San Jose, CA 95128 USA. Alameda Cty Med Ctr, Dept Med, Oakland, CA USA. RP Ward, MM (reprint author), NIAMSD, NIH, US Dept Hlth & Human Serv, Bldg 10,Room 9S205,10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. NR 35 TC 10 Z9 10 U1 3 U2 4 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2003 VL 12 IS 6 BP 443 EP 448 DI 10.1191/0961203303lu410oa PG 6 WC Rheumatology SC Rheumatology GA 697PU UT WOS:000183953100004 PM 12873045 ER PT J AU Dauter, Z AF Dauter, Z TI Protein structures at atomic resolution SO MACROMOLECULAR CRYSTALLOGRAPHY, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID 1.2 ANGSTROM RESOLUTION; X-RAY CRYSTALLOGRAPHY; PANCREATIC TRYPSIN-INHIBITOR; CRYSTAL-STRUCTURE DETERMINATION; INITIO STRUCTURE DETERMINATION; BIOLOGICAL METHANE FORMATION; PHOTOACTIVE YELLOW PROTEIN; LEAST-SQUARES REFINEMENT; MATING PHEROMONE ER-1; LIVIDANS XYLANASE 10A C1 Brookhaven Natl Lab, NCI, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. RP Dauter, Z (reprint author), Brookhaven Natl Lab, NCI, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, Bldg 725,AX9, Upton, NY 11973 USA. NR 267 TC 17 Z9 17 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 368 BP 288 EP 337 DI 10.1016/S0076-6879(03)68016-X PG 50 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY10E UT WOS:000187631200016 PM 14674280 ER PT J AU Nagem, RAP Polikarpov, I Dauter, Z AF Nagem, RAP Polikarpov, I Dauter, Z TI Phasing on rapidly soaked ions SO MACROMOLECULAR CRYSTALLOGRAPHY, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID WAVELENGTH ANOMALOUS SCATTERING; PROTEIN CRYSTAL-STRUCTURES; SIGNAL; LYSOZYME; COMPLEX; BINDING; DOMAIN; TOOL; REFINEMENT; ANGSTROM C1 Unicamp Caixa, CBME, Lab Nacl Luz Sincrotron, BR-13084971 Campinas, SP, Brazil. Unicamp Caixa, Inst Fis Gleb Wataghin, BR-13084971 Campinas, SP, Brazil. Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560 Sao Carlos, SP, Brazil. NCI, Synchroton Radiat Res Stn, Upton, NY 11973 USA. RP Nagem, RAP (reprint author), Unicamp Caixa, CBME, Lab Nacl Luz Sincrotron, BR-13084971 Campinas, SP, Brazil. RI Nagem, Ronaldo/K-3995-2012; Polikarpov, Igor/D-2575-2012; Inst. of Physics, Gleb Wataghin/A-9780-2017; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016 NR 45 TC 15 Z9 15 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 374 BP 120 EP 137 DI 10.1016/S0076-6879(03)74005-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24U UT WOS:000188419600005 PM 14696370 ER PT J AU Jones, DK AF Jones, DK TI Determining and visualizing uncertainty in estimates of fiber orientation from diffusion tensor MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion tensor; eigenvector; uncertainty; tractography ID HUMAN BRAIN; TRACKING; CONNECTIVITY; TISSUES AB Diffusion tensor MRI (DT-MRI) permits determination of the dominant orientation of structured tissue within an image voxel. This has led to the development of 2D graphical methods for representing fiber orientation and DT-MRI "tractography," which aims to reconstruct the 3D trajectories of white matter fasciculi. Most contemporary fiber orientation mapping schemes and tractography algorithms employ the directional information contained in the eigenvectors of the diffusion tensor to approximate white matter fiber orientation. However, while the uncertainty associated with every estimate of an eigenvector has long been recognized, no attempts to quantify this uncertainty in vivo have been reported. Here, a method is proposed for determining confidence intervals in fiber orientation from real DT-MRI data using the bootstrap method. This is used to construct maps of the "cone of uncertainty," allowing simultaneous viewing of fiber orientation and its uncertainty, and to examine the relationship between orientation uncertainty and tissue anisotropy. C1 Inst Psychiat, Sect Old Age Psychiat, London, England. Leicester Royal Infirm, Div Med Phys, Leicester, Leics, England. RP Jones, DK (reprint author), NIH, Rm 3W16E,Bldg 13,13 S Dr, Bethesda, MD 20892 USA. RI Jones, Derek/D-1460-2009; OI Jones, Derek/0000-0003-4409-8049 NR 32 TC 221 Z9 223 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2003 VL 49 IS 1 BP 7 EP 12 DI 10.1002/mrm.10331 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 631BW UT WOS:000180148100002 PM 12509814 ER PT J AU Decking, UKM Pai, VM Wen, H Balaban, RS AF Decking, UKM Pai, VM Wen, H Balaban, RS TI Does binding of Gd-DTPA to myocardial tissue contribute to late enhancement in a model of acute myocardial infarction? SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE myocardial infarction; contrast enhancement; Gd-DPTA; magnetic resonance imaging ID CONTRAST ENHANCEMENT; FUNCTIONAL RECOVERY; MRI AB The long-lasting signal enhancement by Gd-DTPA in areas of myocardial infarction has been conventionally explained by low perfusion and an enhanced Gd distribution volume. To test whether binding of Gd to myocardial constituents is an additional factor contributing to this effect, Gd-DTPA was allowed to equilibrate between homogenized porcine myocardial tissue and physiological saline. The relaxation rate (1/T-1) of homogenate samples (n = 61) increased in proportion (r(2) = 0.98) to the Gd concentration (0.025-0.5 mM) of the surrounding medium, with no evidence for augmented uptake. The diffusion-limited uptake was only slightly more rapid than the subsequent Gd-release. The amount of Gd released was in line with all of the Gd-DTPA in the homogenate participating in water proton relaxation. The data from this acute myocardial infarction model do not support the notion that Gd-DTPA binding in the early stages of myocardial damage contributes to delayed enhancement. Published 2003 Wiley-Liss, Inc.(dagger) C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Decking, UKM (reprint author), Univ Dusseldorf, Dept Cardiovasc Physiol, POB 101007, D-40001 Dusseldorf, Germany. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 NR 11 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2003 VL 49 IS 1 BP 168 EP 171 DI 10.1002/mrm.10324 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 631BW UT WOS:000180148100021 PM 12509833 ER PT B AU Kimber, WI Piao, YL Tanaka, TS Yoshikawa, T Hamatani, T Carter, MG Ko, MSH AF Kimber, WI Piao, YL Tanaka, TS Yoshikawa, T Hamatani, T Carter, MG Ko, MSH GP OECD TI Systematic analysis of mouse preimplantation development SO MAMMALIAN EMBRYO GENOMICS: BIOLOGICAL RESOURCE MANAGEMENT IN AGRICULTURE LA English DT Proceedings Paper CT 1st International Meeting on Mammalian Embryo Genomics CY JUL 20, 2002 CL Quebec City, CANADA ID EQUALIZED CDNA LIBRARY; INITIAL ANNOTATION; CELL-ADHESION; CLONE SET; EMBRYOS; VERIFICATION; CONSTRUCTION; CADHERIN; DESIGN AB Many important and complex events occur during the preimplantation period of mouse development as the embryo transitions from a single totipotent cell to the differentiated structure of the blastocyst. Using an embryogenomics approach, we aim to identify and study genes with key roles in these processes. Our study utilizes the unique resource of the NIA mouse cDNA clone set, which contains many novel, full-length cDNAs representing all mouse preimplantation stages. This clone set provides the basis for microarray experiments enabling us to study global gene expression and assemble gene expression profiles. In addition, we are using EST frequency in individual libraries to identify genes with restricted expression profiles, implying a role at specific stages of preimplantation development. This work is complemented with functional assays including gene "knock-down" experiments using antisense oligo technology. These studies lay the foundation for a systematic evaluation of the role of large numbers of genes in preimplantation development. C1 NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU ORGANIZATION ECONOMIC COOPERATION & DEVELOPMENT PI PARIS PA 2, RUE ANDRE PASCAL, CEDEX 16, 75775 PARIS, FRANCE BN 92-64-10426-7 PY 2003 BP 37 EP 46 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BY65Q UT WOS:000189431500004 ER PT J AU Annilo, T Chen, ZQ Shulenin, S Dean, M AF Annilo, T Chen, ZQ Shulenin, S Dean, M TI Evolutionary analysis of a cluster of ATP-binding cassette (ABC) genes SO MAMMALIAN GENOME LA English DT Article ID FAMILIAL INTRAHEPATIC CHOLESTASIS; MULTIDRUG-RESISTANCE; TANGIER-DISEASE; CYSTIC-FIBROSIS; TRANSPORTER; IDENTIFICATION; DNA; CONVERSIONS; MUTATIONS; SEQUENCES AB To study the evolutionary history of ATP-binding cassette (ABC) transporters in mammals, we have characterized a cluster of five ABCA-subfamily genes localized on mouse Chromosome (Chr) 11. The genes, named Abca5, Abca6, Abca8a, Abca8b, and Abca9, are arranged in a head-to-tail fashion in a cluster that spans about 400 kb of the genomic DNA, each gene occupying about 70 kb. The transcripts of these genes contain an open reading frame from 4863 (for Abca8a and Abca8b) to 4929 for Abca5 nucleotides, and have distinct tissue-specific expression pattern. The predicted proteins contain two transmembrane domains and two nucleotide binding domains, arranged similar to the other members of ABCA subfamily. Similarity of both the genomic organization and primary structure among the genes in this cluster suggests that the duplications generating the cluster occurred relatively recently compared with most of the ABC genes in present-day mammalian genomes. For instance, the Fugu rubripes genome contains an ortholog for only one gene, Abca5, from this cluster. Phylogenetic and comparative sequence analysis reveals that after the divergence of rodent and primate lineages, at least one gene has been lost in each genome. In addition, we found that both mouse and human clusters show evidence of a number of gene conversions, in several cases involving intron sequences. C1 NCI, Lab Genom Divers, Human Genet Sect, Frederick, MD 21702 USA. NCI, Lab Genom Divers, SAIC Frederick, Intramural Res & Support Program, Frederick, MD 21702 USA. RP Annilo, T (reprint author), NCI, Lab Genom Divers, Human Genet Sect, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012; Annilo, Tarmo/J-2900-2013 OI Dean, Michael/0000-0003-2234-0631; Annilo, Tarmo/0000-0002-9588-3058 FU PHS HHS [N01-C0-5600] NR 31 TC 25 Z9 33 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JAN PY 2003 VL 14 IS 1 BP 7 EP 20 DI 10.1007/s00335-002-2229-9 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 634KF UT WOS:000180338000002 PM 12532264 ER PT J AU Angelats, C Wang, XW Jermiin, LS Copeland, NG Jenkins, NA Baker, RT AF Angelats, C Wang, XW Jermiin, LS Copeland, NG Jenkins, NA Baker, RT TI Isolation and characterization of the mouse ubiquitin-specific protease Usp15 SO MAMMALIAN GENOME LA English DT Article ID FAT FACETS GENE; DEUBIQUITINATING ENZYME; FUNCTIONAL-CHARACTERIZATION; SACCHAROMYCES-CEREVISIAE; CHROMOSOMAL LOCALIZATION; CLONING; EXPRESSION; UNP; SEQUENCES; ENCODES AB We have characterized the mouse ortholog of the human ubiquitin-specific protease USP15. Mouse Usp15 consists of 981 amino acids with a predicted molecular mass of 112 kDa, contains the highly conserved Cys and His boxes present in all members of the UBP family of deubiquitinating enzymes, and is 98% identical/99% similar to human USP15. Usp15 shares 59.5% identity/75.5% sequence similarity with the mouse Unp Usp4 oncoprotein. Recombinant Usp15 demonstrated ubiquitin-specific protease activity against engineered linear fusions of ubiquitin to glutathione S-transferase. UspI5 can also cleave the ubiquitin-proline bond, as can USP15 and Usp4. Alignment of mouse and human Usp15 and Usp4 protein sequences suggested that Usp15/USP15 may be alternately spliced in a manner analogous to Usp4. Sequence analysis of RT-PCR products from several human and mouse cell lines and tissues revealed alternate splicing in all cells studied. Northern blot analysis of both mouse and human Usp15 revealed two differently sized mRNAs in all tissues examined, owing to alternate polyadenylation sites spaced by 1.5 kb. Chromosomal mapping by interspecific backcross analysis localized the Usp15 gene to the distal region of mouse Chromosome (Chr) 10. This region is syntenic with human Chr 12q24, the location of human USPI5, and a different location to Unp Usp4) (Chr 9). Identification of the mouse UspI5 gene >69.5 kb and human USP15 gene 145 kb sequences in genome databases reveals that both are composed of 22 exons with identical splice sites, and both have an exon/intron structure identical to the mouse Usp4 gene, including the alternately spliced exon. Phylogenetic studies suggest that a sequence currently identified as a chicken Usp4 ortholog is in fact a USP15 ortholog, while bona-fide chicken, cow, and rat Usp4 orthologs can be identified in EST databases. C1 Australian Natl Univ, John Curtin Sch Med Res, Div Mol Med, Urbiquitin Lab, Canberra, ACT 2601, Australia. Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Baker, RT (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Div Mol Med, Urbiquitin Lab, GPO Box 334, Canberra, ACT 2601, Australia. RI Jermiin, Lars/C-2458-2009 OI Jermiin, Lars/0000-0002-9619-3809 NR 46 TC 14 Z9 16 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JAN PY 2003 VL 14 IS 1 BP 31 EP 46 DI 10.1007/s00335-002-3035-0 PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 634KF UT WOS:000180338000004 PM 12532266 ER PT B AU Olden, K AF Olden, K BE Rapport, DJ Lasley, WL Rolston, DE Nielsen, NO Qualset, CO Damania, AB TI Environmental health research challenges SO MANAGING FOR HEALTHY ECOSYSTEMS LA English DT Proceedings Paper CT International Congress on Managing for Healthy Ecosystems CY AUG 15-20, 1999 CL UNIV CALIF DAVIS, SACRAMENTO, CA HO UNIV CALIF DAVIS C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Olden, K (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LEWIS PUBLISHERS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 USA BN 1-56670-612-2 PY 2003 BP 15 EP 19 PG 5 WC Ecology; Environmental Sciences SC Environmental Sciences & Ecology GA BV80A UT WOS:000180070100003 ER PT J AU Snyder, RV Gibbs, PDL Palacios, A Abiy, L Dickey, R Lopez, JV Rein, KS AF Snyder, RV Gibbs, PDL Palacios, A Abiy, L Dickey, R Lopez, JV Rein, KS TI Polyketide synthase genes from marine dinoflagellates SO MARINE BIOTECHNOLOGY LA English DT Article DE polyketide; polyketide synthase; toxin; dinotlagellate; biosynthesis ID PROROCENTRUM-LIMA; ENGINEERED BIOSYNTHESIS; GONYAULAX-POLYEDRA; OKADAIC ACID; BACTERIA; MICROORGANISMS; STREPTOMYCES; METABOLITES; TOXICITY; SEQUENCE AB Rapidly developing techniques for manipulating the pathways of polyketide biosynthesis at the genomic level have created the demand for new pathways with novel biosynthetic capability. Polyketides derived from dinoflagellates are among the most complex and unique structures identified thus far, yet no studies of the biosynthesis of dinoflagellate-derived polyketides at the genomic level have been reported. Nine strains representing 7 different species of dinoflagellates were screened for the presence of type I and type II polyketide synthases (PKSs) by polymerase chain reaction (PCR) and reverse transcriptase PCR. Seven of the 9 strains yielded products that were homologous with known and putative type I PKSs. Unexpectedly, a PKS gene was amplified from cultures of the dinoflagellate Gymnodinium catenatum, a saxitoxin producer, which is not known to produce a polyketide. In each case the presence of a PKS gene was correlated with the presence of bacteria in the cultures as identified by amplification of the bacterial 16S ribosomal RNA gene. However, amplification from polyadenylated RNA, the lack of PKS expression in light-deprived cultures, residual phylogenetic signals, resistance to methylation-sensitive restriction enzymes, and the lack of hybridization to bacterial isolates support a dinoflagellate origin for most of these genes. C1 Florida Int Univ, Dept Chem, Miami, FL 33199 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Harbor Branch Oceanog Inst Inc, Div Biomed Marine Res, Ft Pierce, FL 34946 USA. RP Rein, KS (reprint author), Florida Int Univ, Dept Chem, 11200 SW 8th St, Miami, FL 33199 USA. EM reink@fiu.edu RI Lopez, Jose/F-8809-2011 OI Lopez, Jose/0000-0002-1637-4125 FU NIEHS NIH HHS [P30 ES05705]; NIGMS NIH HHS [GM 61347, R21 GM60012-01] NR 41 TC 58 Z9 62 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1436-2228 J9 MAR BIOTECHNOL JI Mar. Biotechnol. PD JAN-FEB PY 2003 VL 5 IS 1 BP 1 EP 12 DI 10.1007/s10126-002-0077-y PG 12 WC Biotechnology & Applied Microbiology; Marine & Freshwater Biology SC Biotechnology & Applied Microbiology; Marine & Freshwater Biology GA 651QZ UT WOS:000181333200001 PM 12925913 ER PT S AU Boston, R Stefanovski, D Moate, P Linares, O Greif, P AF Boston, R Stefanovski, D Moate, P Linares, O Greif, P BE Novotny, JA Green, MH Boston, RC TI Cornerstones to shape modeling for the 21(st) century: Introducing the aka-glucose project SO MATHEMATICAL MODELING IN NUTRITION AND THE HEALTH SCIENCES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th Conference on Mathematical Modeling in Nutrition and the Health Sciences CY JUL 29-AUG 01, 2000 CL Penn State Univ, Univ Pk, PA HO Penn State Univ ID KINETIC-ANALYSIS; METABOLISM; SAAM C1 Univ Penn, Sch Vet Med, New Bolton Ctr, Biomath Unit, Kennett Sq, PA 19348 USA. Univ Michigan, Geriatr Clin, Ann Arbor, MI 48105 USA. NCI, Lab Computat & Expt Biol, Div Canc Biol & Diag, Bethesda, MD 20892 USA. RP Boston, R (reprint author), Univ Penn, Sch Vet Med, New Bolton Ctr, Biomath Unit, 382 W St Rd, Kennett Sq, PA 19348 USA. EM boston@cahp2.nbc.upenn.edu OI Moate, Peter/0000-0003-4598-2047 NR 27 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47881-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 537 BP 21 EP 42 PG 22 WC Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Medicine, Research & Experimental; Physiology SC Computer Science; Mathematics; Research & Experimental Medicine; Physiology GA BY63J UT WOS:000189426100002 PM 14995026 ER PT S AU Wastney, ME Pentchev, PG Neufeld, EB AF Wastney, ME Pentchev, PG Neufeld, EB BE Novotny, JA Green, MH Boston, RC TI Fitting a mathematical model to biological data: Intracellular trafficking in Niemann-Pick C disease SO MATHEMATICAL MODELING IN NUTRITION AND THE HEALTH SCIENCES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th Conference on Mathematical Modeling in Nutrition and the Health Sciences CY JUL 29-AUG 01, 2000 CL Penn State Univ, Univ Pk, PA HO Penn State Univ ID DENSITY-LIPOPROTEIN UPTAKE; CHOLESTEROL STORAGE; ACCUMULATION; FIBROBLASTS; ENDOCYTOSIS C1 Metab Modeling Serv Ltd, Hamilton, New Zealand. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20891 USA. RP Wastney, ME (reprint author), Metab Modeling Serv Ltd, POB 23008,Dalesford, Hamilton, New Zealand. EM wastneym@drc.co.nz NR 13 TC 3 Z9 3 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47881-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 537 BP 63 EP 75 PG 13 WC Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Medicine, Research & Experimental; Physiology SC Computer Science; Mathematics; Research & Experimental Medicine; Physiology GA BY63J UT WOS:000189426100004 PM 14995028 ER PT S AU Lewis, KC Hochadel, JF Zech, LA AF Lewis, KC Hochadel, JF Zech, LA BE Novotny, JA Green, MH Boston, RC TI A systems modeling approach to the study of retinoid function: Implications for evaluation of retinoids in cancer chemoprevention and/or chemotherapy SO MATHEMATICAL MODELING IN NUTRITION AND THE HEALTH SCIENCES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th Conference on Mathematical Modeling in Nutrition and the Health Sciences CY JUL 29-AUG 01, 2000 CL Penn State Univ, Univ Pk, PA HO Penn State Univ ID VITAMIN-A STATUS; BREAST-CANCER; PROSTATE-CANCER; FENRETINIDE; RATS; N-(4-HYDROXYPHENYL)RETINAMIDE; METABOLISM; LIVER; TOLERABILITY; PLASMA C1 NCI, Basic Res Lab, Drug Nutr Interact Grp, NIH, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. RP Lewis, KC (reprint author), NCI, Basic Res Lab, Drug Nutr Interact Grp, NIH, Bldg 560,Room 12-27, Frederick, MD 21702 USA. EM lewiskc@mail.ncifcrf.gov NR 33 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47881-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 537 BP 301 EP 316 PG 16 WC Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Medicine, Research & Experimental; Physiology SC Computer Science; Mathematics; Research & Experimental Medicine; Physiology GA BY63J UT WOS:000189426100020 PM 14995044 ER PT S AU Novotny, JA Greif, P Boston, RC AF Novotny, JA Greif, P Boston, RC BE Novotny, JA Green, MH Boston, RC TI WinSAAM: Application and explanation of use SO MATHEMATICAL MODELING IN NUTRITION AND THE HEALTH SCIENCES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th Conference on Mathematical Modeling in Nutrition and the Health Sciences CY JUL 29-AUG 01, 2000 CL Penn State Univ, Univ Pk, PA HO Penn State Univ C1 USDA, BHNRC, DHPL, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NCI, Lab Expt & Computat Biol, Bethesda, MD 20892 USA. Univ Penn, New Bolton Ctr, Dept Clin Studies, Kennett Sq, PA 19348 USA. RP Novotny, JA (reprint author), USDA, BHNRC, DHPL, Beltsville Human Nutr Res Ctr, Bldg 308,Room 201,BARC E, Beltsville, MD 20705 USA. EM novotny@bhnrc.arsusda.gov; novotny@bhnrc.arsusda.gov NR 5 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47881-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 537 BP 343 EP 351 PG 9 WC Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Medicine, Research & Experimental; Physiology SC Computer Science; Mathematics; Research & Experimental Medicine; Physiology GA BY63J UT WOS:000189426100022 PM 14995046 ER PT S AU Boston, RC Sumner, AE AF Boston, RC Sumner, AE BE Novotny, JA Green, MH Boston, RC TI STATA: A statistical analysis system for examining biomedical data SO MATHEMATICAL MODELING IN NUTRITION AND THE HEALTH SCIENCES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 7th Conference on Mathematical Modeling in Nutrition and the Health Sciences CY JUL 29-AUG 01, 2000 CL Penn State Univ, Univ Pk, PA HO Penn State Univ C1 Univ Penn, New Bolton Ctr, Sch Vet Med, Dept Clin Studies, Kennett Sq, PA 19348 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Boston, RC (reprint author), Univ Penn, New Bolton Ctr, Sch Vet Med, Dept Clin Studies, 382 W St Rd, Kennett Sq, PA 19348 USA. EM boston@cahp2.nbc.upenn.edu; boston@cahp2.nbc.upenn.edu NR 4 TC 31 Z9 31 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47881-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 537 BP 353 EP 369 PG 17 WC Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Medicine, Research & Experimental; Physiology SC Computer Science; Mathematics; Research & Experimental Medicine; Physiology GA BY63J UT WOS:000189426100023 PM 14995047 ER PT J AU Simons, RF Detenber, BH Cuthbert, BN Schwartz, DD Reiss, JE AF Simons, RF Detenber, BH Cuthbert, BN Schwartz, DD Reiss, JE TI Attention to television: Alpha power and its relationship to image motion and emotional content SO MEDIA PSYCHOLOGY LA English DT Article ID FRONTAL BRAIN ASYMMETRY; VISUAL-ATTENTION; AFFECTIVE STYLE; SCENE CHANGES; PATTERNS; MEMORY; RESPONSES; AROUSAL; INERTIA; EXPRESSION AB A laboratory experiment investigated the impact of image motion and emotional content in brief television clips on attention. Using an electroencephalogram (EEG) as a measure of attention, cortical activity in 25 participants was measured while they viewed either still or moving emotion-provoking images. Spectral analysis of the EEG was done to gauge changes in alpha-wave (8-13 Hz) power because reductions in alpha power are thought to indicate greater attention. The analysis revealed that subjective reports of emotional arousal were directly related to cortical activation (i.e., reduced alpha power), and this was particularly true at the parietal recording site. The relationship between alpha power and ratings of valence was curvilinear; cortical activation was associated with both positive and negative images relative to neutral images. Alpha power was also reduced during,feet occurred inde-the viewing of moving compared with still images, and this effect pendent of stimulus valence. The association of greater cortical activation with moving than with still images is consistent with previous research using autonomic measures and suggests that image motion modulates emotional responding-and sustains attention-primarily through increasing "gain" in the arousal dimension. C1 Nanyang Technol Univ, Sch Commun & Informat, Singapore 637718, Singapore. Univ Delaware, Dept Psychol, Newark, DE 19716 USA. NIMH, Div Neurosci & Basic Behav Sci, Behav Sci Res Branch, Bethesda, MD USA. Univ Delaware, Dept Psychol, Newark, DE 19716 USA. RP Detenber, BH (reprint author), Nanyang Technol Univ, Sch Commun & Informat, 31 Nanyang Link, Singapore 637718, Singapore. NR 64 TC 24 Z9 25 U1 10 U2 15 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1521-3269 J9 MEDIA PSYCHOL JI Media Psychol. PY 2003 VL 5 IS 3 BP 283 EP 301 DI 10.1207/S1532785XMEP0503_03 PG 19 WC Communication; Film, Radio, Television; Psychology, Applied SC Communication; Film, Radio & Television; Psychology GA 708YE UT WOS:000184597300003 ER PT S AU Tosun, D Rettmann, ME Prince, JL AF Tosun, D Rettmann, ME Prince, JL BE Ellis, RE Peters, TM TI Mapping techniques for aligning sulci across multiple brains SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2003, PT 2 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 6th International Conference on Medical Imaging Computing and Computer-Assisted Intervention CY NOV 15-18, 2003 CL MONTREAL, CANADA SP Robarts Res Inst, No Digital Inc ID CEREBRAL-CORTEX; COORDINATE SYSTEM; CORTICAL SURFACE; MRI AB Visualization and mapping of function on the cortical surface is difficult because of its sulcal and gyral convolutions. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in the literature. This makes visualization and measurement possible, but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. In this paper, we describe an approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way. To quantify how accurately the geometric features - i.e., sulci and gyri - are mapped into the same location, sulcal alignment across multiple brains are analyzed, and probabilistic maps for different sulcal regions are generated to be used in automatic labelling of segmented sulcal regions. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Tosun, D (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. EM duygu@iron.ece.jhu.edu; rettmann@iron.ece.jhu.edu; prince@iron.ece.jhu.edu RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 17 TC 3 Z9 3 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-20464-4 J9 LECT NOTES COMPUT SC PY 2003 VL 2879 BP 862 EP 869 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BY19R UT WOS:000188180400105 ER PT S AU Hsu, LY Rhoads, KL Aletras, AH Arai, AE AF Hsu, LY Rhoads, KL Aletras, AH Arai, AE BE Ellis, RE Peters, TM TI Surface coil intensity correction and non-linear intensity normalization improve pixel-resolution parametric maps of myocardial MRI perfusion SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2003, PT 2 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 6th International Conference on Medical Imaging Computing and Computer-Assisted Intervention CY NOV 15-18, 2003 CL MONTREAL, CANADA SP Robarts Res Inst, No Digital Inc AB We present a systematic approach to generate pixel-wise parametric maps from contrast-enhanced MR myocardial perfusion images. A surface coil intensity correction algorithm is used to compensate the myocardial intensity inhomogeneity. Non-linear intensity normalization is applied to color encode the pixel intensity. The preliminary result shows our technique is valuable in differentiating perfusion defects within myocardial regions of interest. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Hsu, LY (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Aletras, Anthony/0000-0002-3786-3817 NR 2 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-20464-4 J9 LECT NOTES COMPUT SC PY 2003 VL 2879 BP 975 EP 976 PG 2 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BY19R UT WOS:000188180400130 ER PT S AU Yao, JH Taylor, R AF Yao, JH Taylor, R BE Sonka, M Fitzpatrick, JM TI A multiple-layer flexible mesh template matching method for nonrigid registration between a pelvis model and CT images SO MEDICAL IMAGING 2003: IMAGE PROCESSING, PTS 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE Multiple-Layer Flexible mesh template; non-rigid registration AB A robust non-rigid registration method has been developed to deform a pelvis model to match with anatomical structures in a CT image. A statistical volumetric model is constructed from a collection of training CT datasets. The model is represented as a hierarchical tetrahedral mesh equipped with embedded Bernstein polynomial density functions on the barycentric coordinates of each tetrahedron. The prior information of both shape properties and density properties is incorporated in the model. The non-rigid registration process consists of three stages: affine transformation, global deformation, and local deformation. A multiple-layer flexible mesh template matching method is developed to adjust the location of each vertex on the model to achieve an optimal match with the anatomical structure. The mesh template is retrieved directly from the tetrahedral mesh structure, with multiple-layer structure for different scales of anatomical features and flexible searching sphere for robust template matching. An adaptive deformation focus strategy is adopted to gradually deform each vertex to its matched destination. Several constraints are applied to guarantee the smoothness and continuity. A "leave-one-out" validation showed that the method can achieve about 94% volume overlap and 5.5% density error between the registered model and the ground truth model. RP Yao, JH (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 7 TC 4 Z9 4 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4833-8 J9 P SOC PHOTO-OPT INS PY 2003 VL 5032 BP 1117 EP 1124 DI 10.1117/12.481354 PN 1-3 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW90V UT WOS:000183561900121 ER PT S AU Long, LR Antani, S Lee, DJ Krainak, DM Thoma, GR AF Long, LR Antani, S Lee, DJ Krainak, DM Thoma, GR BE Huang, HK Ratib, OM TI Biomedical information from a national collection of spine x-rays: Film to content-based retrieval SO MEDICAL IMAGING 2003: PACS AND INTEGRATED MEDICAL INFORMATION SYSTEMS: DESIGN AND EVALUATION SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE x-ray; multimedia database; Web; CBIR; content-based image retrieval ID SHAPE; RADIOGRAPHS; SYSTEM AB We summarize research and development for the extraction and distribution of biomedical information from a collection of 17,000 spine x-ray images collected by the second National Health and Nutrition Examination Survey (NHANES II). We present a history of the technical milestones of this work, including the data collection as film, digitization, quality control, archiving technology, database organization, medical expert content evaluation, and Web data distribution. We conclude by presenting our current work in content-based image retrieval (CBIR) to exploit the information content of these images directly by using image processing. We provide an overview and current research results from this CBIR. . work, which includes: extensive segmentation research focusing on Active Shape Modeling and Active Contour methods; alternative techniques for shape representation, including invariant moments, simple polygon approximation, and Fourier descriptors; neural network classification of shapes into biomedical categories, such as "anterior osteophytes present/not present"; and the implementation of a prototype CBIR system for the vertebrae that supports hybrid text/image queries using MATLAB and the MySQL relational database system. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 30 TC 12 Z9 12 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4834-6 J9 P SOC PHOTO-OPT INS PY 2003 VL 5033 BP 70 EP 84 DI 10.1117/12.487798 PG 15 WC Computer Science, Information Systems; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91P UT WOS:000183592800009 ER PT S AU Wen, H AF Wen, H BE Yaffe, MK Antonuk, LE TI Non-invasive quantitative mapping of conductivity and dielectric distributions using the RF wave propagation effects in high field MRI SO MEDICAL IMAGING 2003: PHYSICS OF MEDICAL IMAGING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE conductivity; dielectric constant; noninvasive; imaging; tissue; MRI bioimpedance; dielectric resonance ID CURRENT-DENSITY; MAGNETIC-RESONANCE; HEAD AB In this paper I show with phantom and animal experiments a non-invasive and quantitative method for measuring the conductivity and dielectric distributions based on high field magnetic resonance imaging. High field MRI is accompanied by significant RF wave-propagation effects. They are observed as phase and magnitude variations of the image that cannot be removed by optimizing the static field homogeneity, or by improving the RF coils. These variations reflect the RF field distribution in the sample, and in fact obey a modified Helmholtz equation. By mapping both the phase and magnitude of the, field with MRI techniques, both the conductivity and the dielectric constant are determined non-invasively. In phantom experiments at 1.5 tesla, conductivity value were measured at 4 mm resolution to 0.5 S/m accuracy. At 4.7 tesla, the accuracy was improved to 0.2 S/m, and the-dielectric constant was measured to an accuracy of 5 (relative to vacuum) for 2cm regions. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Wen, H (reprint author), NHLBI, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 11 TC 30 Z9 31 U1 1 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4831-1 J9 P SOC PHOTO-OPT INS PY 2003 VL 5030 BP 471 EP 477 DI 10.1117/12.480000 PG 7 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BX07Z UT WOS:000184199600045 ER PT S AU Miller, MT Jerebko, AK Malley, JD Summers, RM AF Miller, MT Jerebko, AK Malley, JD Summers, RM BE Clough, AV Amini, AA TI Feature selection for computer-aided polyp detection using genetic algorithms SO MEDICAL IMAGING 2003: PHYSIOLOGY AND FUNCTION: METHODS, SYSTEMS, AND APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE genetic algorithms; support vector machines; feature selection; forward stepwise search; computer aided diagnosis; virtual colonoscopy ID FEATURE SUBSET-SELECTION AB To improve computer aided diagnosis (CAD) for CT colonography we designed a hybrid classification scheme that uses a committee of support vector machines (SVMs) combined with a genetic algorithm (GA) for variable selection. The genetic algorithm selects subsets of four features, which are later combined to form a committee, with majority vote for classification across the base classifiers. Cross validation was used to predict the accuracy (sensitivity, specificity, and combined accuracy) of each base classifier SVM. As a comparison for GA, we analyzed a popular approach to feature selection called forward stepwise search (FSS). We conclude that genetic algorithms are effective in comparison to the forward search procedure when used in conjunction with a committee of support vector machine classifiers for the purpose of colonic polyp identification. C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Miller, MT (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 20 TC 18 Z9 18 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4832-X J9 P SOC PHOTO-OPT INS PY 2003 VL 5031 BP 102 EP 110 DI 10.1117/12.485796 PG 9 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91N UT WOS:000183592700012 ER PT S AU Callot, V Bennett, E Wen, H AF Callot, V Bennett, E Wen, H BE Clough, AV Amini, AA TI An IVIM based MRI method to study microcirculation in the heart - Preliminary results in dogs. SO MEDICAL IMAGING 2003: PHYSIOLOGY AND FUNCTION: METHODS, SYSTEMS, AND APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE MRI; myocardium; perfusion; IVIM; diffusion; perfusion; micro-circulation; STEAM; blood flow ID MAGNETIC-RESONANCE; WATER DIFFUSION; IN-VIVO; PERFUSION; MYOCARDIUM; RAT; EXCHANGE; FLOW AB in living organs, microcirculation. in the capillaries and high order branches can be seen as a macroscopically random process. The Intra, Voxel Incoherent Motion (IVIM) method uses a diffusion-weighted magnetic resonance imaging sequence to register this pseudo-random motion. It is able to observe perfusion in addition to the brownian diffusion by its relatively large distance of movement. The dependence of the MR signal (S) on the diffusion weighting b can be approximated as a bi-exponential relation: (S/S-0)=(1-f).exp(-bD)+f.exp(-b(D+D*)),. where S-0 is the signal intensity for b=0, f the vascular volume fraction, D the molecular diffusion coefficient and D* a flow index. This effect, largely investigated in the brain, has never been applied in the heart, where the diffusion-weighted sequence is highly sensitive to bulk motion. We have studied microcirculation in the canine heart in vivo, with a well-controlled cardiac and respiratory gating protocol that overcomes the bulk motion effects. We demonstrated that the IVIM effect could be applied in the myocardium. The IVIM parameters were found equal to D=1.26*10(-3) mm(2)/S, f=11.98%, D*=12.87*10(-3) mm(2)/s. Moreover, the microcirculation is directionally anisotropic. The preferred direction of capillaries/small Vessels is aligned with the myofibers in mid-myocardium in the left ventricle. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Callot, V (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,B1D416, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4832-X J9 P SOC PHOTO-OPT INS PY 2003 VL 5031 BP 214 EP 221 DI 10.1117/12.480284 PG 8 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91N UT WOS:000183592700024 ER PT S AU Kemeny, S Ye, F Braun, A AF Kemeny, S Ye, F Braun, A BE Clough, AV Amini, AA TI Arterial spin tagging fMRI in continuous overt speech production compared to BOLD technique SO MEDICAL IMAGING 2003: PHYSIOLOGY AND FUNCTION: METHODS, SYSTEMS, AND APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE fMRI; BOLD; brain mapping; perfusion; language ID EVENT-RELATED FMRI AB Conventional BOLD fMRI has limited use in overt speech paradigms, due to movement and susceptibility artifacts. Our study used an arterial spin-tagging (AST) sequence to quantify focal brain activation in a continuous speech task. Furthermore, we compared the results to conventional BOLD fMRI. The ASSIST sequence was used to obtain transverse perfusion images of the brain, acquired on a 1.5T GE-Signa scanner. Three conditions were alternated in a block design: generation of complete sentences, nonsense syllables and rest with continuous and overt speech production. For 4 normal volunteers, task-related perfusion maps with quantified rCBF and rCBV values were calculated and activations were mapped to the. MNI brain. The same paradigm was scanned with BOLD contrast fMRI in separate,. independent scans and data from 6 subjects were analyzed using SPM99. Using the, AST sequence, we could reliably identify focal brain activation in an overt continuous speech paradigm, and the activations observed were consistent with previous PET studies. We found differential activation at increasing levels of speech production with a focus in the left insula and opercular IFG related to the production of sentences at a syntactic level as opposed to nonsense syllable production.. The BOLD technique failed to identify some of these activation foci, possibly due to decreased SNR and artifacts. C1 NIDCD, NIH, LS, Bethesda, MD 20892 USA. RP Kemeny, S (reprint author), NIDCD, NIH, LS, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4832-X J9 P SOC PHOTO-OPT INS PY 2003 VL 5031 BP 320 EP 323 DI 10.1117/12.480320 PG 4 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91N UT WOS:000183592700035 ER PT S AU Yao, JH Miller, M Franaszek, M Summers, RM AF Yao, JH Miller, M Franaszek, M Summers, RM BE Clough, AV Amini, AA TI Automatic segmentation of colonic polyps in CT colonography based on knowledge-guided deformable models SO MEDICAL IMAGING 2003: PHYSIOLOGY AND FUNCTION: METHODS, SYSTEMS, AND APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE colonic polyp segmentation; fuzzy c-mean cluster; deformable model ID VOLUMETRIC FEATURES AB An automatic method to segment colonic polyps from CT colonography is presented. The method is based on a combination of knowledge-guided intensity adjustment, fuzzy c-mean clustering, and deformable models. The input is a set of polyp seed points generated by filters on geometric properties of the colon surface. First, the potential polyp region is enhanced by a knowledge-guided adjustment. Then, a fuzzy c-mean clustering is applied on a 64*64 pixel sub-image around the seed. Fuzzy membership functions for lumen air, polyp tissues and other tissues are computed for each pixel. Finally, the gradient of the fuzzy membership function is used as the image force to drive a deformable model to the polyp boundary. The segmentation process is first executed on the 2D transverse slice where the polyp seed is located, and then is propagated to neighboring slices to construct a 3D representation of the polyp. Manual segmentation is performed on the same polyps and treated as the ground truth. The automatically generated segmentation is compared with the ground truth segmentation to validate the accuracy of the method. Experimental results showed that the average overlap between the automatic segmentation and manual segmentation is 76.3%. Given the complex polyp boundaries and the small size of the polyp, this is a good result both visually and quantitatively. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 4 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4832-X J9 P SOC PHOTO-OPT INS PY 2003 VL 5031 BP 370 EP 380 DI 10.1117/12.480415 PG 11 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91N UT WOS:000183592700041 ER PT S AU Malley, JD Jerebko, AK Miller, MT Summers, RM AF Malley, JD Jerebko, AK Miller, MT Summers, RM BE Clough, AV Amini, AA TI Variance reduction for error estimation when classifying colon polyps front CT colonography SO MEDICAL IMAGING 2003: PHYSIOLOGY AND FUNCTION: METHODS, SYSTEMS, AND APPLICATIONS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE virtual colonoscopy; classification; error estimation; support vector machines; bias-variance reduction AB For cancer polyp detection based on CT colonography we investigate the sample variance of two methods for estimating the sensitivity and specificity. The goal is the reduction of sample variance for both error estimates, as a first step towards comparison with other detection schemes. Our detection scheme is based on a committee of support vector machines. The two estimates of sensitivity and specificity studied here are a smoothed bootstrap (the 632+ estimator), and ten-fold cross-validation. It is shown that the 632+ estimator generally has lower sample variance, than the usual cross-validation estimator. When the number of nonpolyps in the training set is relatively small we obtain approximately 80% sensitivity and 50% specificity (for either method). On the other hand, when the number of nonpolyps in the training set is relatively large, estimated sensitivity (for either method) drops considerably. Finally, we consider the intertwined roles of relative sample sizes (polyp/nonpolyp), misclassification costs, and bias-variance reduction. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Malley, JD (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4832-X J9 P SOC PHOTO-OPT INS PY 2003 VL 5031 BP 570 EP 578 DI 10.1117/12.485803 PG 9 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91N UT WOS:000183592700063 ER PT J AU Jerebko, AK Summers, RM Malley, JD Franaszek, M Johnson, CD AF Jerebko, AK Summers, RM Malley, JD Franaszek, M Johnson, CD TI Computer-assisted detection of colonic polyps with CT colonography using neural networks and binary classification trees SO MEDICAL PHYSICS LA English DT Article DE colon cancer; neural network; classification tree; computer-assisted diagnosis ID AIDED DIAGNOSIS AB Detection of colonic polyps in CT colonography is problematic due to complexities of polyp shape and the surface of the normal colon. Published results indicate the feasibility of computer-aided detection of polyps but better classifiers are needed to improve specificity. In this paper we compare the classification results of two approaches: neural networks and recursive binary trees. As our starting point we collect surface geometry information from three-dimensional reconstruction of the colon, followed by a filter based on selected variables such as region density, Gaussian and average curvature and sphericity. The filter returns sites that are candidate polyps, based on earlier work using detection thresholds, to which the neural nets or the binary trees are applied. A data set of 39 polyps from 3 to 25 mm in size was used in our investigation. For both neural net and binary trees we use tenfold cross-validation to better estimate the true error rates. The backpropagation neural net with one hidden layer trained with Levenberg-Marquardt algorithm achieved the best results: sensitivity 90% and specificity 95% with 16 false positives per study. (C) 2003 American Association of Physicists in Medicine. C1 NCI, Dept Radiol, Bethesda, MD 20892 USA. NCI, Ctr Informat Technol, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. RP Summers, RM (reprint author), NCI, Dept Radiol, 10 Ctr Dr, Bethesda, MD 20892 USA. EM rms@nih.gov FU NCI NIH HHS [R01CA75333] NR 25 TC 52 Z9 52 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2003 VL 30 IS 1 BP 52 EP 60 DI 10.1118/1.1528178 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 637CG UT WOS:000180493600009 PM 12557979 ER PT J AU Yogeeswari, P Sriram, D Brahmandam, A Sridharan, I Thirumurugan, R Stables, JP AF Yogeeswari, P Sriram, D Brahmandam, A Sridharan, I Thirumurugan, R Stables, JP TI Synthesis of novel aryl semicarbazones as anticonvulsants with GABA-mediated mechanism SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID ANTIEPILEPTIC DRUG DEVELOPMENT; MAXIMAL ELECTROSHOCK SCREEN; GAMMA-AMINOBUTYRIC ACID; 4-AMINO-HEX-5-ENOIC ACID; PHARMACOLOGICAL FACTORS; LABORATORY EVALUATION; SEIZURE MODELS; AMINO GROUP; BRAIN; ARYLSEMICARBAZONES AB A series of 3-bromophenyl semicarbazone derivatives were synthesized and evaluated for anticonvulsant activity. Compound 5e demonstrated to have anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure (scPTZ) tests, the ED50 being 32.35 mg/kg and < 45 mg/kg respectively. The quantitative measurement of gamma-aminobutyric acid (GABA) levels in different regions of the rat brain after administration of the aryl semicarbazone had shown a significant increase in GABA level. These results suggest that aryl semicarbazone derivatives have potential as a new anticonvulsant drug. C1 Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. NIH, Epilepsy Branch, Preclin Pharmacol Sect, Bethesda, MD 20892 USA. RP Yogeeswari, P (reprint author), Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. NR 32 TC 10 Z9 12 U1 0 U2 1 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 2003 VL 12 IS 2 BP 57 EP 68 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 737TX UT WOS:000186248800001 ER PT B AU Bondy, CA Dimitroakakis, C AF Bondy, CA Dimitroakakis, C BE Schneider, HPG TI Androgens and breast cancer risk SO MENOPAUSE: STATE OF THE ART - IN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 10th World Congress on the Menopause CY JUN 10-14, 2002 CL BERLIN, GERMANY SP Int Menopause Soc ID SEX-HORMONE LEVELS; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; ADRENAL-HYPERPLASIA; REPLACEMENT THERAPY; URINARY ANDROGENS; PROSTATE-CANCER; RECEPTOR GENE; SERUM; ESTROGEN C1 NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. NR 54 TC 1 Z9 1 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND BN 1-84214-160-0 PY 2003 BP 28 EP 35 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BW18R UT WOS:000181103000006 ER PT B AU Sberman, S AF Sberman, S BE Schneider, HPG TI Staging system for reproductive aging in women SO MENOPAUSE: STATE OF THE ART - IN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 10th World Congress on the Menopause CY JUN 10-14, 2002 CL BERLIN, GERMANY SP Int Menopause Soc ID FOLLICLE-STIMULATING-HORMONE; MENOPAUSAL TRANSITION; AGE; PERIMENOPAUSE; POPULATION; ESTRADIOL; SYMPTOMS; DYNAMICS; MIDLIFE; LIFE C1 NIA, NIH, Bethesda, MD 20892 USA. RP Sberman, S (reprint author), NIA, NIH, Gateway Bldg,Suite 3E327,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND BN 1-84214-160-0 PY 2003 BP 331 EP 336 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BW18R UT WOS:000181103000057 ER PT J AU Mahady, GB Parrot, J Lee, C Yuri, GS Dan, A AF Mahady, GB Parrot, J Lee, C Yuri, GS Dan, A TI Botanical dietary supplement use in peri- and postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE menopause; botanical dietary supplements; efficacy; safety; information ID HERB-DRUG INTERACTIONS; THERAPIES; WARFARIN AB Objective: To determine use of botanical dietary supplements (BDS) in women between the ages of 40 and 60 years at the University of Illinois at Chicago (UIC) clinics, including information about commonly used BDS, the reason for use, information resources used, and the overall perception of safety and efficacy of BDS. Design: Five hundred female outpatients at UIC clinics were interviewed by healthcare practitioners using a botanical/drug history questionnaire. Respondents were 46.8% African American, 39.6% Caucasian, 11.7% Hispanic, and 1.5% Asian, with a mean age of 50.34 years. Results: BDS were used by 79% of respondents (n = 395), of which 36.5% used BDS daily. Of the positive respondents, 51.7% used one or two BDS, whereas 48.4% used three or more. Commonly used botanicals included soy (42%), green tea (34.68%), chamomile (20.76%), gingko (20.51%), ginseng (17.97%), Echinacea (15.44%), and St. John's wort (7.34%). Black cohosh, garlic, red clover, kava, valerian, evening primrose, and ephedra were used by less than 15% of respondents. Efficacy ratings were high for BDS, and 68% claimed to have no side effects. Only 3% of respondents obtained BDS information from healthcare professionals, and 70% of respondents were not informing their physician of BDS use. Conclusions: A high percentage of women at UIC clinics were using multiple BDS. The respondents believed that these products were both safe and effective for the treatment of common ailments. Concomitant BDS use with prescription and over-the-counter medications was commonplace, often without a physician's knowledge. Consumer education about the possible benefits and risks associated with BDS use is urgently needed. C1 Univ Illinois, Coll Pharm, NIH,Ctr Bot Dietary Supplements Res, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Dept Pharm Practice, Chicago, IL 60612 USA. Univ Illinois, Ctr Excellence Womens Hlth, Chicago, IL 60612 USA. RP Mahady, GB (reprint author), Univ Illinois, Coll Pharm, NIH,Ctr Bot Dietary Supplements Res, Program Collaborat Res Pharmaceut Sci, 833 S Wood St,MC 877, Chicago, IL 60612 USA. FU NCCIH NIH HHS [P50-AT00155-404] NR 19 TC 76 Z9 80 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2003 VL 10 IS 1 BP 65 EP 72 DI 10.1097/01.GME.0000029028.95924.F9 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 635FQ UT WOS:000180388600011 PM 12544679 ER PT J AU Chen, DT Miller, FG Rosenstein, DL AF Chen, DT Miller, FG Rosenstein, DL TI Ethical aspects of research into the etiology of autism SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE autism; research ethics; pedigree; risk factor research; genetics; neuroimaging; research with healthy children; family members as research subjects ID METHODOLOGICAL ISSUES; PEDIGREE RESEARCH; DISORDERS; CHILDREN; CONSENT; PRIVACY AB Advances in understanding autism and other developmental neuropsychiatric disorders will come from an integration of various research strategies including phenomenologic, functional neuroimaging, and pharmacologic methods, as well as epidemiologic approaches aimed at identifying genetic and environmental risk factors. The highly heritable nature of autism makes it scientifically valuable to involve parents and siblings as research participants. However, many studies on autism pose ethical challenges because they do not offer the prospect of direct benefit to subjects. In this article, we present an in-depth ethical analysis of current nontherapeutic research strategies that are common in autism research. The ethical analysis applies a proposed ethical framework for evaluating clinical research focusing on seven ethical requirements: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4) favorable risk-benefit ratio (5) independent review, (6) informed consent, and (7) respect for potentiai and enrolled research participants. (C) 2003 Wiley-Liss, Inc. C1 NIMH, Off Clin Director, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chen, DT (reprint author), NIMH, Off Clin Director, Intramural Res Program, NIH, Bldg 10,Room 3N242,10 Ctr Dr,MSC 1277, Bethesda, MD 20892 USA. NR 23 TC 18 Z9 19 U1 2 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2003 VL 9 IS 1 BP 48 EP 53 DI 10.1002/mrdd.10059 PG 6 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 652NV UT WOS:000181386000009 PM 12587138 ER PT J AU Dvorak, JA AF Dvorak, JA TI The application of atomic force microscopy to the study of living vertebrate cells in culture SO METHODS LA English DT Article DE atomic force microscopy; scanning probe; Dvorak chamber; live cells ID FIELD OPTICAL MICROSCOPY; SCANNING FORCE; SURFACE; CONTRAST AB Atomic force microscopy (AFM), a relatively new variant of scanning probe microscopy developed for the material sciences, is becoming an increasingly important tool in other disciplines. In this review I describe in nontechnical terms some of the basic aspects of using AFM to study living vertebrate cells. Although AFM has some unusual attributes such as an ability to be used with living cells, AFM also has attributes that make its use in cell biology a real challenge. This review was written to encourage researchers in the biological and biomedical sciences to consider AFM as a potential (and potent) tool for their cell biological research. Published by Elsevier Science (USA). C1 NIAID, Lab Malaria & Vector Res, Biophys & Biochem Parasitol Sect, NIH, Bethesda, MD 20892 USA. RP Dvorak, JA (reprint author), NIAID, Lab Malaria & Vector Res, Biophys & Biochem Parasitol Sect, NIH, Bldg 4,Room B2-11,MSC 0425,4 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 37 Z9 42 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JAN PY 2003 VL 29 IS 1 BP 86 EP 96 AR PII S1046-2023(02)00284-0 DI 10.1016/S1046-2023(02)00284-0 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 642RP UT WOS:000180818200009 PM 12543074 ER PT J AU Haux, R McCray, AT AF Haux, R McCray, AT TI Changes in the Editorial Office SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material C1 UMIT Univ Hlth Informat & Technol Tyrol, Inst Hlth Informat Syst, A-6020 Innsbruck, Austria. Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Haux, R (reprint author), UMIT Univ Hlth Informat & Technol Tyrol, Inst Hlth Informat Syst, Innrain 98, A-6020 Innsbruck, Austria. NR 1 TC 1 Z9 1 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2003 VL 42 IS 5 BP 497 EP 498 PG 2 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 760KG UT WOS:000187809700001 ER PT J AU Mitchell, JA McCray, AT Bodenreider, O AF Mitchell, JA McCray, AT Bodenreider, O TI From phenotype to genotype: Issues in navigating the available information resources SO METHODS OF INFORMATION IN MEDICINE LA English DT Article ID 2002 UPDATE; DATABASE; GENOME; ACCESS AB Objectives: As part of an investigation of connecting health professionals and the lay public to both disease and genomic information, we assessed the availability and nature of the data from the Human Genome Project relating to human genetic diseases. Methods: We focused on a set of single gene diseases selected from main topics in MEDLINEplus, the NLM's principal resource focused on consumers. We used publicly available websites to investigate specific questions about the genes and gene products associated with the diseases. We also investigated questions of knowledge and data representation for the information resources and navigational issues. Results: Many online resources are available but they are complex and technical. The major challenges encountered when navigating from phenotype to genotype were (1) complexity of the data, (2) dynamic nature of the data, (3) diversity of foci and number of information resources, and (4) lack of use of standard data and knowledge representation methods. Conclusions: Three major informatics issues arise from the navigational challenges. First, the official gene names are insufficient for navigation of these web resources. Second, navigational inconsistencies arise from difficulties in determining the number and function of alternate forms of the gene or gene product and maintaining currency with this information. Third, synonymy and polysemy cause much confusion. These are severe obstacles to computational navigation from phenotype to genotype, especially for individuals who are novices in the underlying science. Tools and standards to facilitate this navigation are sorely needed. C1 Univ Missouri, Sch Med, Dept Hlth Management & Informat, Columbia, MO 65211 USA. NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mitchell, JA (reprint author), Univ Missouri, Sch Med, Dept Hlth Management & Informat, 325 Clark Hall, Columbia, MO 65211 USA. FU Intramural NIH HHS [Z99 LM999999] NR 21 TC 18 Z9 19 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2003 VL 42 IS 5 BP 557 EP 563 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 760KG UT WOS:000187809700010 PM 14654891 ER PT J AU Lins, U Farina, M Kachar, B AF Lins, U Farina, M Kachar, B TI Membrane vesicles in magnetotactic bacteria SO MICROBIOLOGICAL RESEARCH LA English DT Article DE cell surface ultrastructure; freeze-etching; magnetotactic bacteria; Magnetospirillum; membrane vesicles ID ULTRASTRUCTURE; MAGNETOSOMES AB Magnetotactic bacteria are microorganisms that respond to magnetic fields. We have studied the surface ultrastructure of Magnetospirillum magnetotacticum and uncultured magnetotactic bacteria from a marine environment using transmission electron microscopy and freeze-etching. Numerous membrane vesicles were observed on the surface of Magnetospirillum magnetotacticum bacteria. All uncultured magnetotactic bacteria presented membrane vesicles on their surface in addition to an extensive capsular material and an S-layer formed by particles arranged in a hexagonal symmetry. We did not observe any indication of electron-dense precipitation on the surface of these microorganisms. Our results indicate that membrane vesicles are a common characteristic of magnetotactic bacteria in natural sediments. C1 Univ Fed Rio de Janeiro, Inst Microbiol, Dept Microbiol Geral, BR-21941 Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941590 Rio De Janeiro, Brazil. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Lins, U (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Dept Microbiol Geral, BR-21941 Rio De Janeiro, Brazil. EM ulins@micro.ufrj.br RI Farina, Marcos/I-3744-2014; Lins, Ulysses/N-7282-2015 OI Lins, Ulysses/0000-0002-1786-1144 NR 13 TC 4 Z9 5 U1 0 U2 5 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0944-5013 J9 MICROBIOL RES JI Microbiol. Res. PY 2003 VL 158 IS 4 BP 317 EP 320 DI 10.1078/0944-5013-00210 PG 4 WC Microbiology SC Microbiology GA 760KF UT WOS:000187809600006 PM 14717452 ER PT J AU Kimura, T Wada, A Nakayama, M Ogushi, KI Nishi, Y De Guzman, BB Moss, J Hirayama, T AF Kimura, T Wada, A Nakayama, M Ogushi, KI Nishi, Y De Guzman, BB Moss, J Hirayama, T TI High molecular weight factor in FCS inhibits Helicobacter pylori VacA-binding to its receptor, RPTP beta, on AZ-521 SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Helicobacter pylori; vacuolating cytotoxin; VacA; RPTP beta; toxin receptor ID VACUOLATING CYTOTOXIN; CELLS AB VacA, a secretory product of Helicobacter pylori, binds to its cell surface receptor, receptor tyrosine phosphatase (RPTP) 0, leading to cytoplasmic vacuolization of gastric epithelial AZ-521 cells. VacA binding to the cell surface and VacA-dependent vacuolization were inhibited by cell culture media containing fetal calf serum (FCS). The high molecular weight fraction of FCS isolated by Superose 12 gel filtration chromatography inhibited VacA binding, whereas only weak effects were observed with other fractions. These data show that the high molecular weight fraction of FCS inhibits VacA action though its ability to block toxin binding to its receptor, RPTPbeta, on AZ-521 cells. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan. NR 9 TC 4 Z9 5 U1 0 U2 0 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 4-16 YAYOI 2-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PY 2003 VL 47 IS 1 BP 105 EP 107 PG 3 WC Immunology; Microbiology SC Immunology; Microbiology GA 633FF UT WOS:000180271300014 PM 12636260 ER PT B AU Poodry, CA AF Poodry, Clifton A. GP Natl Acad Press TI Diversity: Why is it important and how can it be achieved? SO MINORITIES IN THE CHEMICAL WORKFORCE: DIVERSITY MODELS THAT WORK LA English DT Proceedings Paper CT Workshop on Minorities in the Chemical Workforce - Diversity Models that Work CY MAR, 2002 CL Washington, DC SP NRC Report Comm C1 Natl Inst Hlth, Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08539-X PY 2003 BP 6 EP 15 PG 10 WC Social Issues SC Social Issues GA BGS29 UT WOS:000250299100001 ER PT S AU Hsu, LY Lin, KP Hu, YC Yamada, N Watabe, H Iida, H AF Hsu, LY Lin, KP Hu, YC Yamada, N Watabe, H Iida, H BE Feng, D Carson, ER TI Motion estimation and correction for myocardial perfusion imaging SO MODELLING AND CONTROL IN BIOMEDICAL SYSTEMS 2003 (INCLUDING BIOLOGICAL SYSTEMS) SE IFAC SYMPOSIA SERIES LA English DT Proceedings Paper CT 5th IFAC Symposium on Modelling and Control in Biomedical Systems CY AUG 21-23, 2003 CL MELBOURNE, AUSTRALIA SP Int Federat Automat Control, IUPESM, IEEE Engn Med & Biol Soc, Int Measurement Confederat, Inst Engineers Australia, Univ Sydney, Hong Kong Polytech Univ DE motion estimation; optical flows; registration ID QUANTIFICATION; TRACKING; RESERVE; MRI AB Motion estimation and correction is an important yet challenge problem in medical image analysis. This paper presents a new approach to estimate and correct motion artifacts in cardiac perfusion image sequences. The method uses a modified optical flow and block-matching technique to estimate the velocity vector between consecutive image frames. The displacement field of each image is corrected and deformed according a total velocity. This technique is applied to sequences of magnetic resonance myocardial perfusion images. Results from quantitative error measurement and time-intensity plots show improvements over original images after the use of this technique. Copyright (C) 2003 IFAC. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI KIDLINGTON PA THE BOULEVARD, LANGFORD LANE,, KIDLINGTON OX5 1GB, OXFORD, ENGLAND SN 0962-9505 BN 0-08-044159-9 J9 IFAC SYMP SERIES PY 2003 BP 157 EP 161 PG 5 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BY50P UT WOS:000189389800030 ER PT J AU Allred, DC Bryant, JL Land, S Paik, S Fisher, ED Julian, T Margolese, R Smith, R Mamounas, EP Osborne, CK Fisher, B Wolmark, N AF Allred, DC Bryant, JL Land, S Paik, S Fisher, ED Julian, T Margolese, R Smith, R Mamounas, EP Osborne, CK Fisher, B Wolmark, N TI Estrogen receptor status as a predictor of the effectiveness of tamoxifen In DCIS: Findings from NSABP protocol B-24 SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Baylor Coll Med, Houston, TX 77030 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA A80 BP 21A EP 21A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100094 ER PT J AU Torres-Cabala, CA Bibbo, M Roberts, DD Panizo, A Merino, MJ AF Torres-Cabala, CA Bibbo, M Roberts, DD Panizo, A Merino, MJ TI Identification of new proteins in the spectrum of thyroid lesions and their application as possible tumor markers in cytology SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. NCI, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 374 BP 84A EP 85A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100387 ER PT J AU Cassarino, DS Auerbach, A Miller, W Sherry, R Duray, PH AF Cassarino, DS Auerbach, A Miller, W Sherry, R Duray, PH TI The effects of gp-100 and tyrosinase vaccination on Nevi in melanoma patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 393 BP 89A EP 89A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100406 ER PT J AU Auerbach, A Ronchetti, R Linehan, WM Merino, MJ AF Auerbach, A Ronchetti, R Linehan, WM Merino, MJ TI Chromogenic in situ hybridization (CISH) of chromosome 7 supports lack of association between colonic lesions and the Birt-Hogg-Dubey syndrome SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 509 BP 113A EP 113A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100520 ER PT J AU Chian-Garcia, CA Torres-Cabala, CA Eyler, R Linehan, WM Merino, MJ AF Chian-Garcia, CA Torres-Cabala, CA Eyler, R Linehan, WM Merino, MJ TI Renal cell carcinoma in children and young adults: A clinicopathological and immunohistochemical study of 14 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 659 BP 145A EP 146A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100669 ER PT J AU Datta, MW Becich, MJ Bosland, MC Dhir, R Kajdacsy-Balla, A Melamed, J Orenstein, J Silver, S Berman, J AF Datta, MW Becich, MJ Bosland, MC Dhir, R Kajdacsy-Balla, A Melamed, J Orenstein, J Silver, S Berman, J TI Ethnicity based analysis of prostatectomy specimens and PSA outcomes: Results of the NCI cooperative prostate cancer tissue resource SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Med Coll Wisconsin, Cooperat Prostate Canc Tissue Resource, Milwaukee, WI 53226 USA. Univ Pittsburgh, Pittsburgh, PA USA. NYU, Sch Med, New York, NY USA. George Washington Univ, Sch Med, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 665 BP 147A EP 147A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100675 ER PT J AU Melamed, J Datta, MW Becich, MJ Bosland, M Dhir, R Kajdacsy-Balla, A Orenstein, J Silver, S Berman, JJ AF Melamed, J Datta, MW Becich, MJ Bosland, M Dhir, R Kajdacsy-Balla, A Orenstein, J Silver, S Berman, JJ TI Prostate cancer pathologic parameters and clinical outcome: Results from the cooperative prostate cancer tissue resource (CPCTR) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NYU, Sch Med, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Pittsburgh, Pittsburgh, PA USA. George Washington Univ, Washington, DC USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 737 BP 162A EP 162A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100747 ER PT J AU Merino, MJ Torres-Cabala, CA Zbar, B Chian-Garcia, C Linehan, WM AF Merino, MJ Torres-Cabala, CA Zbar, B Chian-Garcia, C Linehan, WM TI Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC): Clinical, histopathological and molecular features of the first American families described SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 739 BP 162A EP 162A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100749 ER PT J AU Ronchetti, RD Torres-Cabala, C Chian-Garcia, CA Duray, PH Phillips, J Linehan, WM AF Ronchetti, RD Torres-Cabala, C Chian-Garcia, CA Duray, PH Phillips, J Linehan, WM TI Expression of estrogen receptor alpha and beta, androgen receptor, and glutathione-s-transferase pi in prostatic adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 760 BP 167A EP 167A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100770 ER PT J AU Ronchetti, RD Torres-Cabala, CA Chian-Garcia, CA Eyler, R Linehan, WM Merino, MJ AF Ronchetti, RD Torres-Cabala, CA Chian-Garcia, CA Eyler, R Linehan, WM Merino, MJ TI Detection of chromosome 7 and 17 aneuploidy in type 1 papillary renal cell carcinoma by chromogenic in situ hybridization (CISH). A comparison with other renal cell tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 761 BP 167A EP 167A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100771 ER PT J AU Torres-Cabala, CA Worrell, RA Chian-Garcia, CA Martinez, A Merino, MJ Linehan, WM AF Torres-Cabala, CA Worrell, RA Chian-Garcia, CA Martinez, A Merino, MJ Linehan, WM TI Inmunohistochemical expression of hypoxia-induced mediators and correlation with VHL gene mutation in sporadic clear cell renal cell carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 789 BP 173A EP 173A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720100799 ER PT J AU Rimsza, LM LeBlanc, M Braziel, R Jaramillo, M Miller, TP Staudt, L Grogan, TM Fisher, R AF Rimsza, LM LeBlanc, M Braziel, R Jaramillo, M Miller, TP Staudt, L Grogan, TM Fisher, R TI Loss of major histocompatibility complex (MHC) class II gene expression predicts poor survival in diffuse large B celllymphoma (DLBCL) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Univ Arizona, Tucson, AZ 85724 USA. SW Oncol Grp, Seattle, WA USA. Oregon Hlth Sci Univ, Portland, OR USA. NIH, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1141 BP 250A EP 250A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101151 ER PT J AU Toro, JR Liewehr, DJ Pabby, N Sorbara, L Raffeld, M Steinberg, S Jaffe, ES AF Toro, JR Liewehr, DJ Pabby, N Sorbara, L Raffeld, M Steinberg, S Jaffe, ES TI gamma delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1167 BP 256A EP 256A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101177 ER PT J AU Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES AF Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES TI Investigation of pro-survival pathways by reverse phase protein microurray in follicular lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1190 BP 261A EP 261A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101200 ER PT J AU Quezado, MM Perez, JL Ronchetti, RD Ghatak, NR AF Quezado, MM Perez, JL Ronchetti, RD Ghatak, NR TI Gain of chromosome 7 in ependymomas and medulloblastomas detected by chromogenic in situ hybridization (CISH) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1333 BP 292A EP 292A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101343 ER PT J AU Quezado, MM Ronchetti, RD Harris, C Perez, JL Tavora, F Patrocinio, R Ghatak, N AF Quezado, MM Ronchetti, RD Harris, C Perez, JL Tavora, F Patrocinio, R Ghatak, N TI Correlation of EGFR gene amplification and overexpression by chromogenic in situ hybridization (CISH), and immunohistochemistry in high grade gliomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1334 BP 292A EP 292A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101344 ER PT J AU Quezado, MM Santi, M Patrocinio, RV Romero, ME Perez, JL Tsokos, M Ghatak, NR AF Quezado, MM Santi, M Patrocinio, RV Romero, ME Perez, JL Tsokos, M Ghatak, NR TI Ependymomas express death receptor 4 and death receptor 5 by immunohistochemistry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC 20010 USA. BIOPSE Labs, Fortaleza, Ceara, Brazil. Virginia Commonwealth Univ, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1335 BP 293A EP 293A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101345 ER PT J AU Fetsch, PA Abati, A Morisaki, K Honjo, Y Mittal, K Hewitt, S Bates, SE AF Fetsch, PA Abati, A Morisaki, K Honjo, Y Mittal, K Hewitt, S Bates, SE TI Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY 10016 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1348 BP 295A EP 295A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101358 ER PT J AU Debelenko, LV Romero, M Tsokos, M AF Debelenko, LV Romero, M Tsokos, M TI Expression of anaplastic lymphoma kinase (ALK) protein in pediatric tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1374 BP 301A EP 301A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101384 ER PT J AU Fukuoka, J Fujii, T Dracheva, T Travis, WD Jen, J AF Fukuoka, J Fujii, T Dracheva, T Travis, WD Jen, J TI Association of PGP9.5 staining with cyclin E, Cdk2, histone remodeling proteins in non-small cell lung cancer: Tissue microarray assessment SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1401 BP 306A EP 307A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101411 ER PT J AU Minato, H Fujii, T Hayden, D Franks, T Falk, R Travis, WD AF Minato, H Fujii, T Hayden, D Franks, T Falk, R Travis, WD TI Localized fibrous tumors (LFT) of the pleura: A clinicopathologic study of 217 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1422 BP 311A EP 311A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101432 ER PT J AU Naizhen, X Witschi, H Linnoila, I AF Naizhen, X Witschi, H Linnoila, I TI Co-expression of achaete-scute homolog-1 (ASH1) with calcitonin-gene related peptide (CGRP) and epithelial cell markers during NNK-induced pulmonary carcinogenesis in hamsters SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, NIH, Rockville, MD USA. Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1424 BP 311A EP 312A PG 2 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101434 ER PT S AU Yu, LC Xu, SG Gu, J White, HD Offer, G AF Yu, LC Xu, SG Gu, J White, HD Offer, G BE Sugi, H TI Helical order in myosin filaments and evidence for one ligand inducing multiple myosin conformations SO MOLECULAR AND CELLULAR ASPECTS OF MUSCLE CONTRACTION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 4th Fujihara Seminar on Molecular and Cellular Aspects of Muscle Contraction CY OCT 28-NOV 01, 2002 CL Halcone, JAPAN SP Fujihara Fdn Sci ID RABBIT PSOAS MUSCLE; X-RAY-DIFFRACTION; FLUORESCENCE TEMPERATURE-JUMP; DOT-ATP STATE; CROSS-BRIDGES; SKELETAL-MUSCLE; MOTOR DOMAIN; SKINNED FIBERS; I STATE; VANADATE C1 NIAMS, Lab Muscle Biol, NIH, Bethesda, MD 20892 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ Bristol, Bristol BS8 1TD, Avon, England. RP Yu, LC (reprint author), NIAMS, Lab Muscle Biol, NIH, Bethesda, MD 20892 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47870-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 538 BP 305 EP 316 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BY91Z UT WOS:000189495300029 PM 15098678 ER PT J AU Yang, HS Jansen, AP Komar, AA Zheng, XJ Merrick, WC Costes, S Lockett, SJ Sonenberg, N Colburn, NH AF Yang, HS Jansen, AP Komar, AA Zheng, XJ Merrick, WC Costes, S Lockett, SJ Sonenberg, N Colburn, NH TI The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTERNAL RIBOSOMAL ENTRY; RNA HELICASE ACTIVITY; FACTOR 4G EIF4G; MESSENGER-RNA; SECONDARY STRUCTURE; MALIGNANT TRANSFORMATION; FACTOR EIF-4A; KAPPA-B; CELLS; BOX AB Pdcd4 is a novel transformation suppressor that inhibits tumor promoter-induced neoplastic transformation and the activation of AP-1-dependent transcription required for transformation. A yeast two-hybrid analysis revealed that Pdcd4 associates with the eukaryotic translation initiation factors eIF4AI and eIF4AII. Immunofluorescent confocal microscopy showed that Pdcd4 colocalizes with eIF4A in the cytoplasm. eIF4A is an ATP-dependent RNA helicase needed to unwind 5' mRNA secondary structure. Recombinant Pdcd4 specifically inhibited the helicase activity of eIF4A and eIF4F. In vivo translation assays showed that Pdcd4 inhibited cap-dependent but not internal ribosome entry site (IRES)-dependent translation. In contrast, Pdcd4(D418A), a mutant inactivated for binding to eIF4A, failed to inhibit cap-dependent or IRES-dependent translation or AP-1 transactivation. Recombinant Pdcd4 prevented eIF4A from binding to the C-terminal region of eIF4G (amino acids 1040 to 1560) but not to the middle region of eIF4G(amino acids 635 to 1039). In addition, both Pdcd4 and Pdcd4(D418A) bound to the middle region of eIF4G. The mechanism by which Pdcd4 inhibits translation thus appears to involve inhibition of eIF4A helicase, interference with eIF4A association-dissociation from eIF4G, and inhibition of eIF4A binding to the C-terminal domain of eIF4G. Pdcd4 binding to eIF4A is linked to its transformation-suppressing activity, as Pdcd4-eIF4A binding and consequent inhibition of translation are required for Pdcd4 transrepression of AP-1. C1 NCI, Gene Regulat Sect, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Image Anal Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. McGill Univ, McGill Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada. RP Yang, HS (reprint author), NCI, Gene Regulat Sect, Canc Res Ctr, Bldg 567,Rm 180, Frederick, MD 21702 USA. RI Yang, Hsin-Sheng/A-6419-2008; Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 NR 53 TC 275 Z9 288 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 26 EP 37 DI 10.1128/MCB.23.1.26-37.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000003 PM 12482958 ER PT J AU Vary, JC Gangaraju, VK Qin, J Landel, CC Kooperberg, C Bartholomew, B Tsukiyama, T AF Vary, JC Gangaraju, VK Qin, J Landel, CC Kooperberg, C Bartholomew, B Tsukiyama, T TI Yeast Isw1p forms two separable complexes in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN REMODELING COMPLEX; HISTONE-FOLD PROTEINS; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; GENE-EXPRESSION; IN-VIVO; DATABASE; DISRUPTION; MACHINES; OCTAMER AB There are several classes of ATP-dependent chromatin remodeling complexes, which modulate the structure of chromatin to regulate a variety of cellular processes. The budding yeast, Saccharomyces cerevisiae, encodes two ATPases of the ISWI class, Isw1p and Isw2p. Previously Isw1p was shown to copurify with three other proteins. Here we identify these associated proteins and show that Isw1p forms two separable complexes in vivo (designated Isw1a and Isw1b). Biochemical assays revealed that while both have equivalent nucleosome-stimulated ATPase activities, Isw1a and Isw1b differ in their abilities to bind to DNA and nucleosomal substrates, which possibly accounts for differences in specific activities in nucleosomal spacing and sliding. In vivo, the two Isw1 complexes have overlapping functions in transcriptional regulation of some genes yet distinct functions at others. In addition, these complexes show different contributions to cell growth at elevated temperatures. C1 Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Mol & Cellular Biol Program, Seattle, WA 98195 USA. Univ Washington, Seattle, WA 98195 USA. So Illinois Univ, Sch Med, Dept Biochem & Mol Biol, Carbondale, IL 62901 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tsukiyama, T (reprint author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, POB 19024,1100 Fairview Ave N,Mailstop A1-162, Seattle, WA 98109 USA. RI Gangaraju, Vamsi/F-9243-2010 FU NCI NIH HHS [R01 CA074841, R29 CA074841, CA74841]; NICHD NIH HHS [5T32 HD07183, T32 HD007183]; NIGMS NIH HHS [R01 GM058465, GM48413, R01 GM048413, GM58465] NR 54 TC 83 Z9 88 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 80 EP 91 DI 10.1128/MCB.23.1.80-91.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000008 PM 12482963 ER PT J AU Goo, YH Sohn, YC Kim, DH Kim, SW Kang, MJ Jung, DJ Kwak, E Barlev, NA Berger, SL Chow, VT Roeder, RG Azorsa, DO Meltzer, PS Suh, PG Song, EJ Lee, KJ Lee, YC Lee, JW AF Goo, YH Sohn, YC Kim, DH Kim, SW Kang, MJ Jung, DJ Kwak, E Barlev, NA Berger, SL Chow, VT Roeder, RG Azorsa, DO Meltzer, PS Suh, PG Song, EJ Lee, KJ Lee, YC Lee, JW TI Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR RECEPTOR COACTIVATOR; HISTONE H3 METHYLATION; CREB-BINDING PROTEIN; DEPENDENT TRANSACTIVATION; DROSOPHILA-TRITHORAX; INTERACTION DOMAINS; ER-ALPHA; IN-VIVO; GENE; CLONING AB Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. These include activating signal cointegrator 2 (ASC-2), a recently isolated transcriptional coactivator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors and numerous other transcription factors. In this report, we show that ASC-2 belongs to a steady-state complex of approximately 2 MDa (ASC-2 complex [ASCOM]) in HeLa nuclei. ASCOM contains retinoblastoma-binding protein RBQ-3, alpha/beta-tubulins, and trithorax group proteins ALR-1, ALR-2, HALR, and ASH2. In particular, ALR-1/2 and HALR contain a highly conserved 130- to 140-amino-acid motif termed the SET domain, which was recently implicated in histone H3 lysine-specific methylation activities. Indeed, recombinant ALR-1, HALR, and immunopurified ASCOM exhibit very weak but specific H3-lysine 4 methylation activities in vitro, and transactivation by retinoic acid receptor appears to involve ligand-dependent recruitment of ASCOM and subsequent transient H3-lysine 4 methyllation of the promoter region in vivo. Thus, ASCOM may represent a distinct coactivator complex of nuclear receptors. Further characterization of ASCOM will lead to a better understanding of how nuclear receptors and other transcription factors mediate transcriptional activation. C1 Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea. Kangnung Natl Univ, Div Marie Life Sci, Kangnung 210702, South Korea. Chonnam Natl Univ, Hormone Res Ctr, Kwangju 500757, South Korea. Ewha Womans Univ, Ctr Signaling Res, Div Mol Life Sci, Seoul 120750, South Korea. Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. Natl Univ Singapore, Fac Med, Dept Microbiol, Singapore 117597, Singapore. Wistar Inst Anat & Biol, Mol Genet Program, Philadelphia, PA 19104 USA. Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Lee, YC (reprint author), Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea. RI Suh, Pann-Ghill/F-3610-2010; OI Lee, Kong-Joo/0000-0001-7972-6020 NR 53 TC 143 Z9 149 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 140 EP 149 DI 10.1128/MCB.23.1.140-149.2003 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000013 PM 12482968 ER PT J AU Wagner, KU Krempler, A Qi, YY Park, K Henry, MD Triplett, AA Riedlinger, G Rucker, EB Hennighausen, L AF Wagner, KU Krempler, A Qi, YY Park, K Henry, MD Triplett, AA Riedlinger, G Rucker, EB Hennighausen, L TI Tsg101 is essential for cell growth, proliferation, and cell survival of embryonic and adult tissues SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SUSCEPTIBILITY GENE TSG101; HUMAN BREAST-CANCER; TUMOR SUSCEPTIBILITY; TRANSCRIPTIONAL ACTIVATION; CRE RECOMBINASE; MICE; PROTEIN; P53; ABNORMALITIES; DEFICIENCY AB Tumor susceptibility gene 101 (Tsg101) was identified in a random mutagenesis screen for potential tumor suppressors in NIH 3T3 cells. Altered transcripts of this gene have been detected in sporadic breast cancers and many other human malignancies. However, the involvement of this gene in neoplastic transformation and tumorigenesis is still elusive. Using gene targeting, we generated genetically engineered mice with a floxed allele of Tsg101. We investigated essential functions of this gene in vivo and examined whether the loss of function of Tsg101 results in tumorigenesis. Conventional knockout mice were generated through Cre-mediated excision of the first coding exon in the germ line of mouse mammary tumor virus (MMTV)-Cre transgenic mice. The complete ablation of Tsg101 in the developing embryo resulted in death around implantation. In contrast, mammary gland-specific knockout mice developed normally but were unable to nurse their young as a result of impaired mammogenesis during late pregnancy. Neither heterozygous null mutants nor somatic knockout mice developed mammary tumors after a latency of 2 years. The Cre-mediated deletion of Tsg101 in primary cells demonstrated that this gene is essential for the growth, proliferation, and survival of mammary epithelial cells. In summary, our results suggest that Tsg101 is required for normal cell function of embryonic and adult tissues but that this gene is not a tumor suppressor for sporadic forms of breast cancer. C1 Univ Nebraska, Med Ctr, Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Wagner, KU (reprint author), Univ Nebraska, Med Ctr, Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805,Rm 8009, Omaha, NE 68198 USA. RI Wagner, Kay-Uwe/B-6044-2009 FU NCI NIH HHS [R01 CA093797, CA-93797] NR 40 TC 86 Z9 96 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 150 EP 162 DI 10.1128/MCB.23.1.150-162.2003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000014 PM 12482969 ER PT J AU Ohiro, Y Usheva, A Kobayashi, S Duffy, SL Nantz, R Gius, D Horikoshi, N AF Ohiro, Y Usheva, A Kobayashi, S Duffy, SL Nantz, R Gius, D Horikoshi, N TI Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; SIGNAL-TRANSDUCTION PATHWAYS; ADAPTER PROTEIN DAXX; TATA-BINDING PROTEIN; INDUCED APOPTOSIS; CELL-DEATH; TRANSCRIPTIONAL REPRESSION; INTERACTING PROTEIN; FUNCTION MUTATIONS; FUNCTION PHENOTYPE AB More than 50% of human cancers contain p53 gene mutations and as a result accumulate altered forms of the full-length p53 protein. Although certain tumor types expressing mutant p53 protein have a poor prognostic process, the precise role of mutant p53 protein in highly malignant tumor cells is not well defined. Some p53 mutants, but not wild-type p53, are shown here to interact with Daxx, a Fas-binding protein that activates stress-inducible kinase pathways. Interaction of Daxx with p53 is highly dependent upon the specific mutation of p53. Tumorigenic mutants of p53 bind to Daxx and inhibit Daxx-dependent activation of the apoptosis signal-regulating kinase I stress-inducible kinases and Jun NH2-terminal kinase. Mutant p53 forms complexes with Daxx in cells, and consequently, mutant p53 is able to rescue cells from Daxx-dependent inhibition of proliferation. Thus, the accumulation of mutant p53 in tumor cells may contribute to tumorigenesis by inhibiting stress-inducible kinase pathways. C1 Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO 63108 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. NCI, Radiat Oncol Sci Program, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Horikoshi, N (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiat Oncol, 4511 Forest Pk Blvd, St Louis, MO 63108 USA. RI Ohiro, Yoichi/A-5470-2012 FU NCI NIH HHS [CA75556]; NHLBI NIH HHS [HL62458, R01 HL062458] NR 66 TC 25 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 322 EP 334 DI 10.1128/MCB.23.1.322-344.2003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000029 PM 12482984 ER PT J AU Ambrosino, C Mace, G Galban, S Fritsch, C Vintersten, K Black, E Gorospe, M Nebreda, AR AF Ambrosino, C Mace, G Galban, S Fritsch, C Vintersten, K Black, E Gorospe, M Nebreda, AR TI Negative feedback regulation of MKK6 mRNA stability by p38 alpha mitogen-activated protein kinase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MESSENGER-RNA STABILITY; SIGNAL-TRANSDUCTION PATHWAY; AU-RICH ELEMENTS; MAP KINASE; MAMMALIAN-CELLS; CELLULAR STRESSES; GENE-EXPRESSION; CDNA CLONING; SAP KINASES; HEAT-SHOCK AB p38 mitogen-activated protein (MAP) kinases play an important role in the regulation of cellular responses to all kinds of stresses. The most abundant and broadly expressed p38 MAP kinase is p38alpha, which can also control the proliferation, differentiation, and survival of several cell types. Here we show that the absence of p38alpha correlates with the up-regulation of one of its upstream activators, the MAP kinase kinase MKK6, in p38alpha(-/-) knockout mice and in cultured cells derived from them. In contrast, the expression levels of the p38 activators MKK3 and MKK4 are not affected in p38alpha-deficient cells. The increase in MKK6 protein concentration correlates with increased amounts of MKK6 mRNA in the p38alpha(-/-) cells. Pharmacological inhibition of p38alpha also up-regulates MKK6 mRNA levels in HEK293 cells. Conversely, reintroduction of p38alpha into p38alpha-/- cells reduces the levels of MKK6 protein and mRNA to the normal levels found in wild-type cells. Moreover, we show that the MKK6 mRNA is more stable in p38alpha-/- cells and that the 3'untranslated region of this mRNA can differentially regulate the stability of the lacZ reporter gene in a p38alpha-dependent manner. Our data indicate that p38alpha can negatively regulate the stability of the MKK6 mRNA and thus control the steady-state concentration of one of its upstream activators. C1 European Mol Biol Lab, D-69117 Heidelberg, Germany. NIA, Lab Cellular & Mol Biol, IRP, NIH, Baltimore, MD 21224 USA. RP Nebreda, AR (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany. NR 71 TC 55 Z9 57 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 1 BP 370 EP 381 DI 10.1128/MCB.23.1.370-381.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628AR UT WOS:000179970000033 PM 12482988 ER PT J AU Mendrysa, SM McElwee, MK Michalowski, J O'Leary, KA Young, KM Perry, ME AF Mendrysa, SM McElwee, MK Michalowski, J O'Leary, KA Young, KM Perry, ME TI mdm2 is critical for inhibition of p53 during lymphopoiesis and the response to ionizing irradiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WILD-TYPE P53; IN-VIVO; DNA-DAMAGE; V(D)J RECOMBINATION; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; P53-DEFICIENT MICE; ONCOPROTEIN MDM2; TUMOR SPECTRUM; EXPRESSION AB The function of the p53 tumor suppressor protein must be highly regulated because p53 can cause cell death and prevent tumorigenesis. In cultured cells, the p90(MDM2) protein blocks the transcriptional activation domain of p53 and also stimulates the degradation of p53. Here we provide the first conclusive demonstration that p90(MDM2) constitutively regulates p53 activity in homeostatic tissues. Mice with a hypomorphic allele of mdm2 revealed a heretofore unknown role for mdm2 in lymphopoiesis and epithelial cell survival. Phenotypic analyses revealed that both the transcriptional activation and apoptotic functions of p53 were increased in these mice. However, the level of p53 protein was not coordinately increased, suggesting that p90(MDM2) can inhibit the transcriptional activation and apoptotic functions of p53 in a manner independent of degradation. Cre-mediated deletion of mdm2 caused a greater accumulation of p53, demonstrating that p90(MDM2) constitutively regulates both the activity and the level of p53 in homeostatic tissues. The observation that only a subset of tissues with activated p53 underwent apoptosis indicates that factors other than p90(MDM2) determine the physiological consequences of p53 activation. Furthermore, reduction of mdm2 in vivo resulted in radiosensitivity, highlighting the importance of mdm2 as a potential target for adjuvant cancer therapies. C1 Univ Wisconsin, Sch Med, Dept Oncol, Madison, WI 53706 USA. Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. RP Perry, ME (reprint author), NCI, Canc Cell Biol Branch, Div Canc Biol, Suite 5000,6130 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-07175, CA-09135, CA-14520, CA-70718, P30 CA014520, T32 CA009135]; NIGMS NIH HHS [GM-07215, T32 GM007215] NR 61 TC 169 Z9 173 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 2 BP 462 EP 473 DI 10.1128/MCB.23.2.462-473.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 632VE UT WOS:000180243500004 PM 12509446 ER PT J AU Sukhodolets, KE Hickman, AB Agarwal, SK Sukhodolets, MV Obungu, VH Novotny, EA Crabtree, JS Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ AF Sukhodolets, KE Hickman, AB Agarwal, SK Sukhodolets, MV Obungu, VH Novotny, EA Crabtree, JS Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ TI The 32-kilodalton subunit of replication protein A interacts with menin, the product of the MEN1 tumor suppressor gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; SINGLE-STRANDED-DNA; NUCLEOTIDE EXCISION-REPAIR; TRANSCRIPTIONAL REPRESSION; COMPLEX-FORMATION; MAMMALIAN-CELLS; FACTOR RPA; BINDING; TYPE-1; P53 AB Menin is a 70-kDa protein encoded by MEN1, the tumor suppressor gene disrupted in multiple endocrine neoplasia type 1. In a yeast two-hybrid system based on reconstitution of Ras signaling, menin was found to interact with the 32-kDa subunit (RPA2) of replication protein A (RPA), a heterotrimeric protein required for DNA replication, recombination, and repair. The menin-RPA2 interaction was confirmed in a conventional yeast two-hybrid system and by direct interaction between purified proteins. Menin-RPA2 binding was inhibited by a number of menin missense mutations found in individuals with multiple endocrine neoplasia type 1, and the interacting regions were mapped to the N-terminal portion of menin and amino acids 43 to 171 of RPA2. This region of RPA2 contains a weak single-stranded DNA-binding domain, but menin had no detectable effect on RPA-DNA binding in vitro. Menin bound preferentially in vitro to free RPA2 rather than the RPA heterotrimer or a subcomplex consisting of RPA2 bound to the 14-kDa subunit (RPA3). However, the 70-kDa subunit (RPA1) was coprecipitated from HeLa cell extracts along with RPA2 by menin-specific antibodies, suggesting that menin binds to the RPA heterotrimer or a novel RPA1-RPA2-containing complex in vivo. This finding was consistent with the extensive overlap in the nuclear localization patterns of endogenous menin, RPA2, and RPA1 observed by immunofluorescence. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Sukhodolets, KE (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 9C-101,10 Ctr Dr,MSC 1802, Bethesda, MD 20892 USA. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 68 TC 83 Z9 84 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 2 BP 493 EP 509 DI 10.1128/MCB.23.2.493-509.2003 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 632VE UT WOS:000180243500007 PM 12509449 ER PT J AU Engel, FB Hauck, L Boehm, M Nabel, EG Dietz, R von Harsdorf, R AF Engel, FB Hauck, L Boehm, M Nabel, EG Dietz, R von Harsdorf, R TI P21 (CIP1) controls proliferating cell nuclear antigen level in adult cardiomyocytes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CYCLIN-DEPENDENT KINASES; CARDIAC GENE-TRANSCRIPTION; INHIBITS DNA-REPLICATION; VENTRICULAR MYOCYTES; MYOCARDIAL-INFARCTION; MUSCLE-CELLS; FREE SYSTEM; PROTEIN; PCNA; DIFFERENTIATION AB Cell cycle withdrawal associated with terminal differentiation is responsible for the incapability of many organs to regenerate after injury. Here, we employed a cell-free system to analyze the molecular mechanisms underlying cell cycle arrest in cardiomyocytes. In this assay, incubation of S phase nuclei mixed with cytoplasmic extract of S phase cells and adult primary cardiomyocytes results in a dramatic reduction of proliferating cell nuclear antigen (PCNA) protein levels. This effect was blocked by the proteasome inhibitors MG132 and lactacystin, whereas actinomycin D and cycloheximide had no effect. Immunodepletion and addback experiments revealed that the effect of cardiomyocyte extract on PCNA protein levels is maintained by p21 but not p27. In serum-stimulated cardiomyocytes PCNA expression was reconstituted, whereas the protein level of p21 but not that of p27 was reduced. Cytoplasmic extract of serum-stimulated cardiomyocytes did not influence the PCNA protein level in S phase nuclei. Moreover, the hypertrophic effect of serum stimulation was blocked by ectopic expression of p21 and the PCNA protein level was found to be upregulated in adult cardiomyocytes derived from p21 knockout mice. Our data provide evidence that p21 regulates the PCNA protein level in adult cardiomyocytes, which has implications for cardiomyocyte growth control. C1 Humboldt Univ, Max Delbruck Ctr Mol Med, Dept Cardiol, Berlin, Germany. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP von Harsdorf, R (reprint author), Humboldt Univ, Klinikum Charite, Med Klin Schwerpunkt Kardiol, Augustenburger Pl 1, D-13353 Berlin, Germany. RI Engel, Felix/A-1767-2008 OI Engel, Felix/0000-0003-2605-3429 NR 65 TC 44 Z9 45 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2003 VL 23 IS 2 BP 555 EP 565 DI 10.1128/MCB.23.2.555-565.2003 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 632VE UT WOS:000180243500012 PM 12509454 ER PT J AU Tuli, R Seghatoleslami, MR Tuli, S Wang, ML Hozack, WJ Manner, PA Danielson, KG Tuan, RS AF Tuli, R Seghatoleslami, MR Tuli, S Wang, ML Hozack, WJ Manner, PA Danielson, KG Tuan, RS TI A simple, high-yield method for obtaining multipotential mesenchymal progenitor cells from trabecular bone SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE mesenchymal progenitor cell; human trabecular bone; tissue engineering; isolation procedure; in vitro cell culture ID ALKALINE-PHOSPHATASE; IN-VITRO; STEM-CELLS; MINERAL DENSITY; INVITRO; MARROW; EXPRESSION; DIFFERENTIATION; PROLIFERATION; OSTEOCALCIN AB In vitro cultures of primary, human trabecular bone-derived cells represent a useful system for investigation of the biology of osteoblasts. Our recent discovery of the multilineage mesenchymal differentiation potential of trabecular bone-derived cells suggests the potential application of these cells as mesenchymal progenitors for tissue repair and regeneration. Such applications are crucially dependent on efficient cell-isolation protocols to yield cells that optimally proliferate and differentiate. In this study, we describe a simple, high-yield procedure, requiring minimal culture expansion, for the isolation of mesenchymal progenitor cells from human trabecular bone. Moreover, these cells retain their ability to differentiate along multiple mesenchymal lineages through successive subculturing. Cell populations isolated and cultured as described here allow the efficient acquisition of a clinically significant number of cells, which may be used as the cell source for tissue-engineering applications. C1 NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Orthoped Surg, Washington, DC USA. Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. NR 47 TC 60 Z9 63 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JAN PY 2003 VL 23 IS 1 BP 37 EP 49 DI 10.1385/MB:23:1:37 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 635FN UT WOS:000180388400005 PM 12611268 ER PT J AU Yanagihara, K Mizuuchi, K AF Yanagihara, K Mizuuchi, K TI Progressive structural transitions within Mu transpositional complexes SO MOLECULAR CELL LA English DT Article ID DNA-BINDING; INVITRO TRANSPOSITION; STRAND CLEAVAGE; ACTIVE-SITE; A-PROTEIN; B-PROTEIN; PHAGE; TRANSPOSOSOME; DOMAINS; ENDS AB Assembly of the Mu transpososome is dependent on specific binding sites for the MuA transposase near the ends of the phage genome. MuA also contacts terminal nucleotides but only upon transpososome assembly, and base-specific recognition of the terminal nucleotides is critical for assembly. We show that Mu ends lacking the terminal 5 bp can form transpososomes, while longer DNA substrates with mutated terminal nucleotides cannot. The impact of the mutations can be suppressed by base mismatches near the end of Mu. Deletion of the flanking strands or mutation of the terminal nucleotides has differential effects on the cleavage and strand transfer reactions. These results show that the terminal nucleotides control the assembly and activation of transpososomes by influencing conformational changes around the active site. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mizuuchi, K (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 35 TC 11 Z9 11 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN PY 2003 VL 11 IS 1 BP 215 EP 224 DI 10.1016/S1097-2765(02)00796-7 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 643EL UT WOS:000180848900023 PM 12535534 ER PT S AU Ghosh, SC Zhu, XX Secchi, A Sadhukhan, SK Girdhar, NK Gourdon, A AF Ghosh, SC Zhu, XX Secchi, A Sadhukhan, SK Girdhar, NK Gourdon, A BE Reimers, JR Picconatto, CA Ellenbogen, JC Shashidhar, R TI Molecular landers as probes for molecular device-metal surface interactions SO MOLECULAR ELECTRONICS III SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th United-Engineering-Foundation Conference on Molecular Electronics, Science and Technology CY DEC 15-19, 2002 CL KEY WEST, FL SP United Engn Fdn Inc, Def Adv Res Projects Lab, Naval Res Lab, MITRE Corp DE molecular landers; STM; single molecule conformation; surface restructuring ID SCANNING-TUNNELING-MICROSCOPY; ORGANIC-MOLECULES; WIRE; ADSORPTION; JUNCTIONS; CU(110); ROUTE AB Specifically designed series of molecules (landers), comprising a central rigid polyaromatic core and several spacers that decouple the board from the metallic surface, have been synthesiied. UHV-STM studies, on one hand, have shown important distortions of the molecule by interaction with the substrate. On the other hand, surface restructuring results from the presence of the molecules. C1 CNRS, CEMES, Grp Nanosci, F-31055 Toulouse 4, France. Texas Med Ctr, MD Anderson Canc Ctr, Houston, TX USA. NIA, NIH, Drug Design & Dev, Baltimore, MD USA. Univ Parma, Dipartimento Chim Organ & Ind, Parma, Italy. Chembiotek Res PVT Ltd, Kolkata, W Bengal, India. RP CNRS, CEMES, Grp Nanosci, BP4347,29 Rue J Marvig, F-31055 Toulouse 4, France. EM gourdon@cemes.fr RI Gourdon, Andre/C-9799-2009; Secchi, Andrea/G-2554-2012 OI Gourdon, Andre/0000-0002-0370-1019; Secchi, Andrea/0000-0003-4045-961X NR 29 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-488-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1006 BP 82 EP 93 DI 10.1196/annals.1292.005 PG 12 WC Engineering, Environmental; Materials Science, Multidisciplinary; Multidisciplinary Sciences; Physics, Applied SC Engineering; Materials Science; Science & Technology - Other Topics; Physics GA BY31R UT WOS:000188893600006 PM 14976011 ER PT J AU Brooks, AI Chattopadhyay, S Mitchison, HM Nussbaum, RL Pearce, DA AF Brooks, AI Chattopadhyay, S Mitchison, HM Nussbaum, RL Pearce, DA TI Functional categorization of gene expression changes in the cerebellum of a Cln3-knockout mouse model for Batten disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Batten disease; neuronal ceroid lipofuscinoses; CLN3; microarrays; gene expression; neurodegeneration; cerebellum ID MITOCHONDRIAL ATP SYNTHASE; SUBUNIT-C; CLN3 PROTEIN; LOCALIZATION; LYSOSOMES; STORAGE; CLUES AB Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten Disease) is the most common progressive neurodegenerative disorder of childhood. The disease is inherited in an autosomal recessive manner and is the result of mutations in the CLN3 gene. One brain region severely affected in Batten disease is the cerebellum. Using a mouse model for Batten disease which shares pathological similarities to the disease in humans we have used oligonucleotide arrays to profile approximately 19,000 mRNAs in the cerebellum. We have identified reproducible changes of twofold or more in the expression of 756 gene products in the cerebellum of 10-week-old Cln3-knockout mice as compared to wild-type controls. We have subsequently divided these genes with altered expression into 14 functional categories. We report a significant alteration in expression of genes associated with neurotransmission, neuronal cell structure and development, immune response and inflammation, and lipid metabolism. An apparent shift in metabolism toward gluconeogenesis is also evident in Cln3-knockout mice. Further experimentation will be necessary to understand the contribution of these changes in expression to a disease state. Detailed analysis of the functional consequences of altered expression of genes in the cerebellum of the Cln3-knockout mice may provide valuable clues in understanding the molecular basis of the pathological mechanisms underlying Batten disease. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Rochester, Ctr Aging & Dev Biol, Sch Med & Dent, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Ctr Funct Genom, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. UCL Royal Free & UCL Med Sch, Dept Paediat & Child Hlth, London WC1E 655, England. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. RP Pearce, DA (reprint author), Univ Rochester, Ctr Aging & Dev Biol, Sch Med & Dent, Rochester, NY 14642 USA. EM david_pearce@urmc.rochester.edu RI Mitchison, Hannah/C-1891-2008 FU NINDS NIH HHS [NS40580] NR 19 TC 24 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2003 VL 78 IS 1 BP 17 EP 30 AR PII S1096-7192(02)00201-9 DI 10.1016/S1096-7192(02)00201-9 PG 14 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 645YP UT WOS:000181008300003 PM 12559844 ER PT B AU Amano, T Fu, LZ Ishizuya-Oka, A Shi, YB AF Amano, T Fu, LZ Ishizuya-Oka, A Shi, YB BE Shi, Y Cidlowski, JA Scott, D Wu, JR Shi, YB TI Thyroid hormone-induced apoptosis during amphibian metamorphosis SO MOLECULAR MECHANISMS OF PROGRAMMED CELL DEATH LA English DT Proceedings Paper CT 2nd International Symposium on Programmed Cell Death CY SEP 01-03, 2002 CL Shanghai, PEOPLES R CHINA SP NICHHD, NIEHS, Amer Red Cross, Univ Med & Dent NJ Robert Wood Johnson Med Sch, Chinese Acad Sci, Shanghai Inst Biol Sci DE Xenopus laevis; thyroid hormone receptor; extracellular matrix (ECM); matrix metalloproteinase (MMP) ID INTESTINAL CONNECTIVE-TISSUE; TADPOLE TAIL REGRESSION; XENOPUS-LAEVIS; MATRIX METALLOPROTEINASES; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; RECEPTOR SUPERFAMILY; FROG METAMORPHOSIS; EPIDERMAL-CELLS; RESPONSE GENES AB Anuran metamorphosis involves thyroid hormone (TH)-induced, systematic transformations of individual organs. The vast majority of the larval tissues are removed during this process. Among them is the complete degeneration of the tail and gills and reduction of small intestine by about 90% (lengthwise). Various morphological and cellular studies have shown that the removal of larval organs/tissues is through programmed cell death or apoptosis. Recent cloning and characterization of TH-regulated genes revealed that a group of genes encoding matrix metalloproteinases (MMPs) are activated by TH during metamorphosis in various organs. The activation of MMPs, which are extracellular or membrane-associated enzymes capable of degrading extracellular matrix (ECM) proteins, are in agreement with the previously observed remodeling/degradation of the ECM during metamorphosis. In vivo and in vitro studies have provided evidence to support that ECM remodeling by MMPs plays an important role in regulating apoptosis and cell migration during tissue remodeling. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Amano, T (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. NR 56 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-47778-5 PY 2003 BP 9 EP 19 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BAR63 UT WOS:000223268200002 ER PT B AU Chuang, DM Hough, C AF Chuang, DM Hough, C BE Shi, Y Cidlowski, JA Scott, D Wu, JR Shi, YB TI Neuroprotection against apoptosis - What has it got to do with the mood stabilizer lithium? SO MOLECULAR MECHANISMS OF PROGRAMMED CELL DEATH LA English DT Proceedings Paper CT 2nd International Symposium on Programmed Cell Death CY SEP 01-03, 2002 CL Shanghai, PEOPLES R CHINA SP NICHHD, NIEHS, Amer Red Cross, Univ Med & Dent NJ Robert Wood Johnson Med Sch, Chinese Acad Sci, Shanghai Inst Biol Sci DE excitotoxicity; Huntington's disease; lithium; neuroprotection; stroke ID CEREBRAL CORTICAL-NEURONS; AP-1 DNA-BINDING; SUBGENUAL PREFRONTAL CORTEX; CEREBELLAR GRANULE CELLS; N-TERMINAL KINASE; GLUTAMATE EXCITOTOXICITY; RAT STRIATUM; MITOCHONDRIAL RELEASE; SIGNAL-TRANSDUCTION; NEUROTROPHIC FACTOR AB Lithium, a mood-stabilizer, robustly protects cultured rat brain neurons against a variety of apoptotic insults including glutamate-induced excitotoxicity. This neuroprotection involves inactivation of the N-methyl-D-aspartate receptors, presumably through reduced phosphorylation of Tyr1472 in the NR2B subunit. Lithium also up-regulates cytoprotective Bcl-2, but down-regulates proapoptotic p53 and Bax. In addition, it activates the cell survival PI-3 kinase/Akt pathway and suppresses glutamate-induced activation of mitogen-activated protein kinase signaling. Release of brain-derived neurotrophic factor and activation of its receptor, TrkB, is a prerequisite for lithium protection against excitotoxicity. In an animal model of acute stroke, post-insult lithium treatment at therapeutic levels reduces ischemia-induced brain infarction and improves behavioral outcome. Lithium also reduces brain damage induced by intra-striatal infusion of an excitotoxin. Collectively, our results suggest that lithium might have clinical utility for the treatment of excitotoxicity-related neurodegeneration. C1 NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorder Program, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorder Program, NIH, 10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. NR 50 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-47778-5 PY 2003 BP 145 EP 154 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BAR63 UT WOS:000223268200013 ER PT J AU Kammermeier, PJ Davis, MI Ikeda, SR AF Kammermeier, PJ Davis, MI Ikeda, SR TI Specificity of metabotropic glutamate receptor 2 coupling to G proteins SO MOLECULAR PHARMACOLOGY LA English DT Article ID N-TYPE CALCIUM; RAT SYMPATHETIC NEURONS; LONG-TERM POTENTIATION; 2ND INTRACELLULAR LOOP; BETA-GAMMA-SUBUNITS; PERTUSSIS-TOXIN; ALPHA-SUBUNIT; SIGNAL TRANSDUCTION; NEUROTRANSMITTER RECEPTORS; BINDING PROTEIN AB Metabotropic glutamate receptor 2 (mGluR2) is a class 3 G protein-coupled receptor and an important mediator of synaptic activity in the central nervous system. Previous work demonstrated that mGluR2 couples to pertussis toxin (PTX)-sensitive G proteins. However, the specificity of mGluR2 coupling to individual members of the G(i/o) family is not known. Using heterologously expressed mGluR2 in rat sympathetic neurons from the superior cervical ganglion (SCG), the mGluR2/G protein coupling profile was characterized by reconstituting coupling in PTX-treated cells expressing PTX-insensitive mutant Galpha proteins and Gbetagamma. By employing this method, it was demonstrated that mGluR2 coupled strongly with Galpha(ob), Galpha(i1), Galpha(i2), and Galpha(i3), although coupling to Galpha(oa) was less efficient. In addition, mGluR2 did not seem to couple to the most divergent member of the G(i/o) family, Galpha(z), although Galpha(z) coupled strongly to the endogenous alpha2 adrenergic receptor. To determine which Galpha proteins may be natively expressed in SCG neurons, the presence of mRNA for various Galpha proteins was tested using reverse transcription-polymerase chain reaction. Strong bands were detected for all members of the G(i/o) family (Galpha(o), Galpha(i1), Galpha(i2),Galpha(i3),Galpha(z)) as well as for Galpha(11) and Galpha(s). A weak signal was detected for Galpha(q) and no Galpha(15) mRNA was detected. C1 NIAAA, Lab Mol Physiol, NIH, Rockville, MD 20852 USA. NIAAA, Lab Integrated Neurosci, NIH, Rockville, MD 20852 USA. RP Kammermeier, PJ (reprint author), NE Ohio Univ, Coll Med, Dept Neurobiol & Pharmacol, 4209 State Route 44,POB 95, Rootstown, OH 44272 USA. RI Davis, Margaret/F-4165-2010; OI Davis, Margaret/0000-0002-0489-8351; Ikeda, Stephen/0000-0002-4088-9508 FU NIGMS NIH HHS [GM56180]; NINDS NIH HHS [NS37615, NS10943] NR 42 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2003 VL 63 IS 1 BP 183 EP 191 DI 10.1124/mol.63.1.183 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 626JV UT WOS:000179868900022 PM 12488551 ER PT J AU Mezey, E AF Mezey, E TI The fate of neural crest stem cells: nature vs nurture SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID PROGENITOR C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 2 BP 129 EP 130 DI 10.1038/sj.mp.4001300 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 649FG UT WOS:000181195900002 ER PT J AU Grafman, J AF Grafman, J TI Anger is a wind that blows out the light of the mind (old proverb) SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; AGGRESSIVE-BEHAVIOR; VIOLENCE; MURDERERS; CHILDREN C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,MSC 1440, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 9 TC 1 Z9 1 U1 6 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 2 BP 131 EP 132 DI 10.1038/sj.mp.4001256 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 649FG UT WOS:000181195900003 PM 12610642 ER PT J AU Heinz, A Jones, DW Gorey, JG Bennet, A Suomi, SJ Weinberger, DR Higley, JD AF Heinz, A Jones, DW Gorey, JG Bennet, A Suomi, SJ Weinberger, DR Higley, JD TI Serotonin transporter availability correlates with alcohol intake in non-human primates SO MOLECULAR PSYCHIATRY LA English DT Article DE disposition to alcoholism; alcohol response; molecular neuroimaging; beta-CIT SPECT; aggressiveness ID I-123 BETA-CIT; NONHUMAN-PRIMATES; DOPAMINE; ASSOCIATION; RECEPTORS; ADDICTION; BEHAVIOR; MONKEYS; ABUSE AB A low level of alcohol intoxication upon initial exposure and impulsive aggressiveness predispose humans to alcoholism. In non-human primates, central serotonin transporter availability and turnover rate were associated with aggressive behavior and a low response to initial alcohol exposure. We assessed the respective effects of these factors on alcohol intake in a free choice paradigm. Serotonin transporter availability in the raphe area, the origin of central serotonergic projections, was measured with single-photon emission computed tomography and the radioligand [I-123]beta-CIT in 11 rhesus monkeys with low and high central serotonin turnover. The amount of alcohol intake in the 3-month observation period was positively correlated with serotonin transporter availability (R=0.76, P=0.006), but not with aggressiveness (R=0.19, P=0.6) or alcohol response upon first exposure (R=-0.48, P=0.2). In a linear multiple regression analysis with serotonin transporter availability, alcohol response, and aggressiveness as independent variables, 82% of the variance of alcohol intake was explained and serotonin transporter availability emerged as the only statistically significant factor (beta=7.81, P=0.006). These observations indicate that there may be a direct relationship between serotonin transporter availability and alcohol intake after controlling for aggression and alcohol response on first exposure. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, DICBR, Bethesda, MD 20892 USA. NICHD, Comparat Ethol Lab, Bethesda, MD USA. RP Heinz, A (reprint author), Humboldt Univ, Charite, Dept Psychiat, Schumannstr 20-21, D-10117 Berlin, Germany. NR 19 TC 46 Z9 47 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 2 BP 231 EP 234 DI 10.1038/sj.mp.4001214 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 649FG UT WOS:000181195900017 PM 12610656 ER PT J AU Bergen, AW van den Bree, MBM Yeager, M Welch, R Ganjei, JK Haque, K Bacanu, S Berrettin, WH Grice, DE Goldman, D Bulik, CM Klump, K Fichter, M Halmi, K Kaplan, A Strober, M Treasure, J Woodside, B Kaye, WH AF Bergen, AW van den Bree, MBM Yeager, M Welch, R Ganjei, JK Haque, K Bacanu, S Berrettin, WH Grice, DE Goldman, D Bulik, CM Klump, K Fichter, M Halmi, K Kaplan, A Strober, M Treasure, J Woodside, B Kaye, WH TI Candidate genes for anorexia nervosa in the 1 p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa SO MOLECULAR PSYCHIATRY LA English DT Article DE anorexia nervosa; serotonin; opioid; gene; association; linkage ID TERM WEIGHT RESTORATION; POPULATION-BASED TWIN; EATING DISORDERS; BULIMIA-NERVOSA; CHROMOSOMAL LOCALIZATION; CONTROLLED FAMILY; FEEDING-BEHAVIOR; MAJOR DEPRESSION; D-FENFLURAMINE; SUSCEPTIBILITY AB Serotonergic and opioidergic neurotransmitter system alterations have been observed in people with eating disorders; the genes for the serotonin 1D receptor (HTR1D) and the opioid delta receptor (OPRD1) are found on chrlp36.3-34.3, a region identified by our group in a linkage analysis of anorexia nervosa (AN). These candidate genes were evaluated for sequence variation and for linkage and association of this sequence variation to AN in family and case: control data sets. Resequencing of the HTR1D locus and a portion of the OPRD1 locus identified novel SNPs and confirmed existing SNPs. Genotype assay development and genotyping of nine SNPs (four at HTR1D and five at OPRD1) was performed on 191 unrelated individuals fulfilling DSM-lV criteria (w/o amenorrhea criterion) for AN, 442 relatives of AN probands and 98 psychiatrically screened controls. Linkage analysis of these candidate gene SNPs with 33 microsatellite markers in families including relative pairs concordantly affected with restricting AN (N=37) substantially increased the evidence for linkage of this region to restricting AN to an NPL score of 3.91. Statistically significant genotypic, allelic, and haplotypic association to AN in the case: control design was observed at HTR1D and OPRD1 with effect sizes for individual SNPs of 2.63 (95% CI=1.21-5.75) for HTR1 D and 1.61 (95% Cl = 1.11-1-2.44) for OPRD1. Using genotype data on parents and AN probands, three SNPs at HTR1D were found to exhibit significant transmission disequilibrium (P<0.05). The combined statistical genetic evidence suggests that HTR1D and OPRD1 or linked genes may be involved in the etiology of AN. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Eating Disorders Module,Western Psychiat Inst & C, Pittsburgh, PA 15213 USA. Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. NIAAA, Rockville, MD 20852 USA. Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Hosp Behav Med, Klin Roseneck, Munich, Germany. Cornell Univ, New York Presbyterian Hosp Westchester, Weill Med Coll, White Plains, NY USA. Toronto Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Los Angeles, CA USA. Bethlem Royal & Maudsley Hosp, Inst Psychiat, London, England. RP Kaye, WH (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Eating Disorders Module,Western Psychiat Inst & C, 3811 OHara St,600 Iroquois Bldg, Pittsburgh, PA 15213 USA. RI turton, miranda/F-4682-2011; Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644; Treasure, Janet/0000-0003-0871-4596 NR 56 TC 71 Z9 71 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 4 BP 397 EP 406 DI 10.1038/sj.mp.4001318 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 674QE UT WOS:000182646800008 PM 12740597 ER PT J AU Weickert, CS Hyde, TM Lipska, BK Herman, MM Weinberger, DR Kleinman, JE AF Weickert, CS Hyde, TM Lipska, BK Herman, MM Weinberger, DR Kleinman, JE TI Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Review DE neurotrophin; TrkB ligand; DLPFC; post-mortem; BDNF; growth factor ID BDNF MESSENGER-RNA; NIGROSTRIATAL DOPAMINERGIC FUNCTION; MEDIODORSAL THALAMIC NUCLEUS; FETAL VENTRAL MESENCEPHALON; DENDRITIC SPINE DENSITY; POSTNATAL RAT-BRAIN; GABAERGIC NEURONS; GENE-EXPRESSION; GLUTAMATE RECEPTORS; MULTIPLE PROMOTERS AB Anatomical and molecular abnormalities of excitatory neurons in the dorsolateral prefrontal cortex (DLPFC) are found in schizophrenia. We hypothesized that brain-derived neurotrophic factor (BDNF), a protein capable of increasing pyramidal neuron spine density and augmenting synaptic efficacy of glutamate, may be abnormally expressed in the DLPFC of patients with schizophrenia. Using an RNase protection assay and Western blotting, we detected a significant reduction in BDNF mRNA (mean = 23%) and protein (mean = 40%) in the DLPFC of patients with schizophrenia compared to normal individuals. At the cellular level, BDNF mRNA was expressed at varying intensities in pyramidal neurons throughout layers II, III, V, and VI of DLPFC. In patients with schizophrenia; neuronal BDNF expression was decreased in layers III, V and VI. Our study demonstrates a reduction in BDNF production and availability in the DLPFC of schizophrenics, and suggests that intrinsic cortical neurons, afferent neurons, C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Weickert, CS (reprint author), 10 Center Dr,Bldg 10-4N312,MSC 1385, Bethesda, MD 20892 USA. RI Shannon Weickert, Cynthia/G-3171-2011; Lipska, Barbara/E-4569-2017 NR 131 TC 309 Z9 322 U1 2 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 6 BP 592 EP 610 DI 10.1038/sj.mp.4001308 PG 19 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 699RD UT WOS:000184069000003 PM 12851636 ER PT J AU Chen, H Wang, N Huo, Y Sklar, P MacKinnon, DF Potash, JB McMahon, F Antonarakis, SE DePaulo, JR Ross, CA McInnis, MG AF Chen, H Wang, N Huo, Y Sklar, P MacKinnon, DF Potash, JB McMahon, F Antonarakis, SE DePaulo, JR Ross, CA McInnis, MG TI Trapping and sequence analysis of 1138 putative exons from human chromosome 18 SO MOLECULAR PSYCHIATRY LA English DT Article DE exon trapping; gene identification; genome; BLAST; bipolar disorder ID BIPOLAR AFFECTIVE-DISORDER; CHROMOSOME 18Q21; GENE-CLUSTER; HUMAN GENOME; REGION; LINKAGE; LOCUS; MAP; IDENTIFICATION; PREDICTION AB In a search for novel genes on chromosome 18 (HC18), on which several regions have been linked to bipolar disorder, we applied exon trapping to HC18-specific cosmids. Among the 1138 exons trapped, 1052 of them have been mapped to HC18, and the remaining 86 have not been localized. No exons were localized to genomic regions other than HC18. BLAST database search revealed that 190 exons were identical to 98 Unigenes on HC18; 98 identical to additional 82 clusters of ESTs not present in the HC18 Unigene set; 39 homologous to genes from human and other species (e < 10(-3)); and the remaining 811 exons had no significant homology to transcripts in public databases. The mapped exons were compared to the 867 annotated genes on HC18 in the Celera databases; 216 exons were identical to 104 Celera 'genes' and the remaining 836 exons were not found in the Celera databases. On average, there were two exons for a matched transcript ( known genes and ESTs). Therefore, the 850 novel exons may represent hundreds of novel genes on chromosome 18. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21278 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21278 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Geneva, Sch Med, Div Med Genet, CH-1211 Geneva, Switzerland. RP Chen, H (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 4-141,600 N Wolfe St, Baltimore, MD 21278 USA. EM hc@jhmi.edu; mmcinnis@jhmi.edu RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; Antonarakis, Stylianos/N-8866-2014; OI McInnis, Melvin/0000-0002-0375-6247; Antonarakis, Stylianos/0000-0001-8907-5823; McMahon, Francis/0000-0002-9469-305X NR 33 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 6 BP 619 EP 623 DI 10.1038/sj.mp.4001288 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 699RD UT WOS:000184069000005 PM 12851638 ER PT J AU Tzavaral, ET Bymaster, FP Felder, CC Wade, M Gomeza, J Wess, J McKinzie, DL Nomikos, GG AF Tzavaral, ET Bymaster, FP Felder, CC Wade, M Gomeza, J Wess, J McKinzie, DL Nomikos, GG TI Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice SO MOLECULAR PSYCHIATRY LA English DT Article DE acetylcholine; M2/M4 muscarinic; microdialysis; hippocampus; passive avoidance; knockout mice ID SCOPOLAMINE-INDUCED AMNESIA; IN-VIVO MICRODIALYSIS; RAT HIPPOCAMPUS; PASSIVE-AVOIDANCE; CORTICAL ACETYLCHOLINE; RELEASE; MEMORY; HABITUATION; ANTAGONIST; CORTEX AB Among the five different muscarinic receptors that have been cloned and characterized, M2 and M4 receptors are localized both post- and presynaptically and are believed to have a pronounced autoreceptor role. The functional importance of these receptors in the regulation of acetylcholine release in the hippocampus and in cognitive processes was investigated by using M2 and M4 receptor single knockout (KO) as well as M2/M4 receptor double KO mice. We found profound alterations in acetylcholine homeostasis in the hippocampus of both M2- and M4-KO mice as well as of the combined M2/M4-KOs, as assessed by in vivo microdialysis. Basal acetylcholine efflux in the hippocampus was significantly increased in M4-KO and was elevated further in M2/M4-KOs. The increase in hippocampal acetylcholine induced by local administration of scopolamine was markedly reduced in M2-KO and completely abolished in M2/M4-KOs. In M2-KO and much more in M2/M4-KOs, the increase in hippocampal acetylcholine triggered by exposure to a novel environment was more pronounced both in amplitude and duration, with a similar trend observed for M4-KOs. Dysregulation of cholinergic function in the hippocampus, as it could result from perturbed autoreceptor function, may be associated with cognitive deficits. Importantly, M2- and M2/M4-KO, but not M4-KO, animals showed an impaired performance in the passive avoidance test. Together these results suggest a crucial role for muscarinic M2 and M4 receptors in the tonic and phasic regulation of acetylcholine efflux in the hippocampus as well as in cognitive processes. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Nomikos, GG (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, DC0510, Indianapolis, IN 46285 USA. NR 54 TC 79 Z9 83 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 7 BP 673 EP 679 DI 10.1038/sj.mp.4001270 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 705ZU UT WOS:000184427800006 PM 12874603 ER PT J AU Wijsman, EM Rosenthal, EA Hall, D Blundell, ML Sobin, C Heath, SC Williams, R Brownstein, MJ Gogos, JA Karayiorgou, M AF Wijsman, EM Rosenthal, EA Hall, D Blundell, ML Sobin, C Heath, SC Williams, R Brownstein, MJ Gogos, JA Karayiorgou, M TI Genome-wide scan in a large complex pedigree with predominantly male schizophrenics from the island of Kosrae: evidence for linkage to chromosome 2q SO MOLECULAR PSYCHIATRY LA English DT Article DE population isolate; linkage analysis; complex trait; schizophrenia; chromosome 2q ID OBSESSIVE-COMPULSIVE DISORDER; FAMILY-BASED ASSOCIATION; GENETIC-VARIATION; SUSCEPTIBILITY LOCI; FOUNDER POPULATIONS; EXTENDED PEDIGREES; OLIGOGENIC TRAITS; RISK-FACTORS; DISEQUILIBRIUM; STRATEGIES AB It is widely accepted that founder populations hold promise for mapping loci for complex traits. However, the outcome of these mapping efforts will most likely depend on the individual demographic characteristics and historical circumstances surrounding the founding of a given genetic isolate. The 'ideal' features of a founder population are currently unknown. The Micronesian islandic population of Kosrae, one of the four islands comprising the Federated States of Micronesia (FSM), was founded by a small number of settlers and went through a secondary genetic 'bottleneck' in the mid-19th century. The potential for reduced etiological (genetic and environmental) heterogeneity, as well as the opportunity to ascertain extended and statistically powerful pedigrees makes the Kosraen population attractive for mapping schizophrenia susceptibility genes. Our exhaustive case ascertainment from this islandic population identified 32 patients who met Ill criteria for schizophrenia or schizoaffective disorder. Three of these were siblings in one nuclear family, and 27 were from a single large and complex schizophrenia kindred that includes a total of 251 individuals. One of the most startling findings in our ascertained sample was the great difference in male and female disease rates. A genome-wide scan provided initial suggestive evidence for linkage to markers on chromosomes 1, 2, 3, 7, 13, 15, 19, and X. Follow-up multipoint analyses gave additional support for a region on 2q37 that includes a schizophrenia locus previously identified in another small genetic isolate, with a well-established recent genealogical history and a small number of founders, located on the eastern border of Finland. In addition to providing further support for a schizophrenia susceptibility locus at 2q37, our results highlight the analytic challenges associated with extremely large and complex pedigrees, as well as the limitations associated with genetic studies of complex traits in small islandic populations. C1 Rockefeller Univ, Human Neurogenet Lab, New York, NY 10021 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Ctr Natl Genotypage, Evry, France. Kosrae Dept Hlth Serv, Kosrae, Micronesia. NIMH, Genet Lab, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Ctr Neurobiol & Behav, Dept Physiol & Cellular Biophys, New York, NY USA. RP Karayiorgou, M (reprint author), Rockefeller Univ, Human Neurogenet Lab, 1230 York Ave,Box 313, New York, NY 10021 USA. RI Brownstein, Michael/B-8609-2009; Heath, Simon/J-4138-2012; OI Sobin, Christina/0000-0002-2117-2034 FU NIMH NIH HHS [MH61399] NR 76 TC 39 Z9 39 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 7 BP 695 EP 705 DI 10.1038/sj.mp.4001356 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 705ZU UT WOS:000184427800009 PM 12874606 ER PT J AU Schulze, TG Hardy, J McMahon, FJ AF Schulze, TG Hardy, J McMahon, FJ TI Inconsistent designs of association studies: a missed opportunity SO MOLECULAR PSYCHIATRY LA English DT Letter ID FAMILY-BASED ASSOCIATION; LINKAGE DISEQUILIBRIUM; ALZHEIMER-DISEASE; BIPOLAR DISORDER; GUIDELINES; GENOME; LOCUS C1 NIMH, Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Schulze, TG (reprint author), NIMH, Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009; Hardy, John/C-2451-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X NR 20 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 9 BP 770 EP 772 DI 10.1038/sj.mp.4001329 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 717JA UT WOS:000185084300001 PM 12931204 ER PT J AU Halim, ND Weickert, CS McClintock, BW Hyde, TM Weinberger, DR Kleinman, JE Lipska, BK AF Halim, ND Weickert, CS McClintock, BW Hyde, TM Weinberger, DR Kleinman, JE Lipska, BK TI Presynaptic proteins in the prefrontal cortex of patients with schizophrenia and rats with abnormal prefrontal development SO MOLECULAR PSYCHIATRY LA English DT Article DE hippocampus; VAMP; syntaxin; synaptophysin; SNAP-25; synaptobrevin; GAP-43; animal model ID NEONATAL HIPPOCAMPAL DAMAGE; SEVERE MENTAL-ILLNESS; SYNAPTOPHYSIN GENE-EXPRESSION; CHRONIC HALOPERIDOL TREATMENT; CORTICAL PYRAMIDAL NEURONS; DENDRITIC SPINE DENSITY; ANTERIOR FRONTAL-CORTEX; MESSENGER-RNA; SYNAPTIC PROTEINS; CEREBRAL-CORTEX AB Dysfunction of the prefrontal cortex in schizophrenia may be associated with abnormalities in synaptic structure and/or function and reflected in altered concentrations of proteins in presynaptic terminals and involved in synaptic plasticity ( synaptobrevin/vesicle-associated membrane protein ( VAMP), synaptosomal-associated protein-25 (SNAP-25), syntaxin, synaptophysin and growth-associated protein-43 (GAP-43)). We examined the immunoreactivity of these synapse-associated proteins via quantitative immunoblotting in the prefrontal cortex of patients with schizophrenia ( n = 18) and in normal controls ( n = 23). We also tested the stability of these proteins across successive post-mortem intervals in rat brains ( at 0, 3, 12, 24, 48, and 70 h). To investigate whether experimental manipulation of prefrontal cortical development in the rat alters prefrontal synaptic protein levels, we lesioned the ventral hippocampus of rats on postnatal day 7 and measured immunoreactivity of presynaptic proteins in the prefrontal cortex on postnatal day 70. VAMP immunoreactivity was lower in the schizophrenic patients by 22% (P<0.03). There were no differences in the immunoreactivity of any other proteins measured in schizophrenic patients as compared to the matched controls. Proteins were fairly stable up to 24 h and thereafter the abundance of most proteins examined was significantly reduced ( falling to as low as 20% of baseline levels at 48-70 h). VAMP immunoreactivity was higher in the lesioned rats as compared to sham controls by 22% ( P<0.03). There were no significant differences between the lesioned rats and sham animals in any other presynaptic protein. These data suggest that apparently profound prefrontal cortical dysfunction in schizophrenia, as well as in an animal model of schizophrenia, may exist without gross changes in the abundance of many synaptic proteins but discrete changes in selected presynaptic molecules may be present. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), 10 Ctr Dr,Bldg 10,Rm 4N306, Bethesda, MD 20892 USA. RI Shannon Weickert, Cynthia/G-3171-2011; Lipska, Barbara/E-4569-2017 NR 76 TC 79 Z9 88 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 9 BP 797 EP 810 DI 10.1038/sj.mp.4001319 PG 14 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 717JA UT WOS:000185084300004 PM 12931207 ER PT J AU Ozaki, N Goldman, D Kaye, WH Plotnicov, K Greenberg, BD Lappalainen, J Rudnick, G Murphy, DL AF Ozaki, N Goldman, D Kaye, WH Plotnicov, K Greenberg, BD Lappalainen, J Rudnick, G Murphy, DL TI Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype SO MOLECULAR PSYCHIATRY LA English DT Article DE genetics; obsessive-compulsive disorder; autism; anorexia; constitutive activation ID OBSESSIVE-COMPULSIVE DISORDER; PROTEIN GENE SLC6A4; REGULATORY REGION; ANOREXIA-NERVOSA; SOCIAL PHOBIA; POLYMORPHISM; FAMILY; AUTISM; PREVALENCE; LOCALIZATION AB Two common serotonin transporter (SERT) untranslated region gene variants have been intensively studied, but remain inconclusively linked to depression and other neuropsychiatric disorders. We now report an uncommon coding region SERT mutation, Ile425Val, in two unrelated families with OCD and other serotonin-related disorders. Six of the seven family members with this mutation had OCD (n=5) or obsessive-compulsive personality disorder (n=1) and some also met diagnostic criteria for multiple other disorders (Asperger's syndrome, social phobia, anorexia nervosa, tic disorder and alcohol and other substance abuse/dependence). The four most clinically affected individuals-the two probands and their two slbs-had the I425V SERT gene gain-of-function mutation and were also homozygous for 50-UTR SERT gene variant with greater transcriptional efficacy. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Fujita Hlth Univ, Sch Med, Dept Psychiat, Aichi, Japan. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Butler Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Dept Psychiat, Providence, RI 02912 USA. Yale Univ, Sch Med, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41,MSC 1264,10 Ctr Dr, Bethesda, MD 20892 USA. RI Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 32 TC 173 Z9 181 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 11 BP 933 EP 936 DI 10.1038/sj.mp.4001365 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 741JA UT WOS:000186453900008 PM 14593431 ER PT J AU Willeit, M Praschak-Rieder, N Neumeister, A Zill, P Leisch, F Stastny, J Hilger, E Thierry, N Konstantinidis, A Winkler, D Fuchs, K Sieghart, W Aschauer, H Ackenheil, M Bondy, B Kasper, S AF Willeit, M Praschak-Rieder, N Neumeister, A Zill, P Leisch, F Stastny, J Hilger, E Thierry, N Konstantinidis, A Winkler, D Fuchs, K Sieghart, W Aschauer, H Ackenheil, M Bondy, B Kasper, S TI A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE melancholic; atypical; mood disorders; nosology; genetics ID POPULATION-BASED SAMPLE; FUNCTIONAL POLYMORPHISM; FEMALE TWINS; AVAILABILITY; REGION; EXPRESSION; GENOTYPE; BINDING; MOOD AB Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression. C1 Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. Univ Hosp Psychiat, Dept Gen Psychiat, Vienna, Austria. NIMH, Inst Hlth, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. Univ Munich, Univ Hosp Psychiat, Dept Neurochem, Munich, Germany. Univ Technol, Dept Stat & Probabil Theory, Vienna, Austria. Brain Res Inst, Div Biochem & Mol Biol, Vienna, Austria. RP Willeit, M (reprint author), Ctr Addict & Mental Hlth, 250 Coll St, Toronto, ON M5T 1R8, Canada. RI Leisch, Friedrich/A-6977-2013; Sieghart, Werner/A-4877-2013 OI Leisch, Friedrich/0000-0001-7278-1983; Sieghart, Werner/0000-0002-0443-0302 NR 32 TC 65 Z9 67 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2003 VL 8 IS 11 BP 942 EP 946 DI 10.1038/sj.mp.4001392 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 741JA UT WOS:000186453900010 PM 14593433 ER PT J AU Hardy, J AF Hardy, J TI Impact of genetic analysis on Parkinson's disease research SO MOVEMENT DISORDERS LA English DT Article; Proceedings Paper CT Workshop on Parkinsonism and Dementia CY MAY 09-11, 2002 CL ISTANBUL, TURKEY SP Movement Disorder Soc, European Sect DE synuclein; parkin; Parkinson's disease; genetics; ubiquitin hydrolase; proteasone ID ALPHA-SYNUCLEIN; LEWY BODIES; MUTATIONS; DEMENTIA; FAMILIES AB Genetic analysis is changing our view of Parkinson's disease: not only is it challenging the long-cherished views about the diagnosis of the disease, it is also starting to suggest a biochemical pathway to disease pathogenesis. These developments are reviewed in the context of three known (synuclein, parkin, and DJ-1) and one suspected (ubiquitin hydrolase) genes for the disease. (C) 2003 Movement Disorder Society. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. UCL, Sch Med, Reta Lila Weston Inst Neurol Studies, London W1N 8AA, England. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10,Room 6C103,MSC1589, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov NR 17 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PY 2003 VL 18 SU 6 BP S96 EP S98 DI 10.1002/mds.10569 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 724XW UT WOS:000185514400014 PM 14502662 ER PT J AU Uhl, GR AF Uhl, GR TI Dopamine transporter: Basic science and human variation of a key molecule for dopaminergic function, locomotion, and parkinsonism SO MOVEMENT DISORDERS LA English DT Review DE neurotransmitter; Parkinson's disease; localization ID DEFICIT HYPERACTIVITY DISORDER; COCAINE ANALOG RECOGNITION; GENE POLYMORPHISM 1215A/G; BETA-ADRENERGIC-RECEPTOR; STRIATAL SYNAPTOSOMES; VARIABLE NUMBER; LIGAND-BINDING; NEUROTRANSMITTER TRANSPORTERS; MONOAMINE TRANSPORTERS; ENHANCES TRANSCRIPTION AB We review the basic science of the dopamine transporter (DAT). a key neurotransmitter for locomotor control and reward systems. including those lost or deranged in Parkinson's disease (PD). Physiology. pharmaceutical features, expression, cDNA, protein structure/function relationships, and phosphorylation and regulation are discussed. The localization of DAT provides the best marker for the integrity of just the presynaptic dopaminergic systems that are most affected in PD. Its function is key for the actions of several toxins that provide some of the best current models for idiopathic parkinsonism, and its variation can clearly alter movement. The wealth of information about this interesting molecule that has been developed over the last 12 years has led to increased interest in DAT among workers interested in both normal and abnormal movement. (C) 2003 Movement Disorder Society. C1 NIDA IRP, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA IRP, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. NR 115 TC 50 Z9 50 U1 3 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PY 2003 VL 18 SU 7 BP S71 EP S80 DI 10.1002/mds.10578 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 734NZ UT WOS:000186064600012 PM 14531049 ER PT J AU Snyderwine, EG Yoon, HS Knight-Jones, LP Tran, M Schut, HAJ Yu, MS AF Snyderwine, EG Yoon, HS Knight-Jones, LP Tran, M Schut, HAJ Yu, MS TI Mutagenesis and DNA adduct formation in the mouse mammary gland exposed to 2-hydroxyamino-1-methyl-6-phenylimidazo-[4,5-b]pyridine in whole organ culture SO MUTAGENESIS LA English DT Article ID SPRAGUE-DAWLEY RATS; IN-VIVO MUTATIONS; EPITHELIAL-CELLS; BREAST-CANCER; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; NEOPLASTIC TRANSFORMATION; HETEROCYCLIC AMINES; COOKED MEAT; CARCINOGEN; RISK AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagen and rodent mammary gland carcinogen found in the human diet. 2-Hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP) is the proximate reactive metabolite of PhIP associated with PhIP-DNA adduct formation and mutagenesis. In the current study, whole mammary glands obtained from transgenic C57Bl/6 mice carrying the plasmid-lacZ mutational reporter gene were cultured in defined medium and exposed to various concentrations of N-hydroxy-PhIP for 24 h. At various times after N-hydroxy-PhIP exposure, PhIP-DNA adduct levels were determined by the P-32-post-labeling assay and the lacZ(-) mutant frequency determined by the positive selection system. Glands were cultured in either medium containing insulin (I medium), necessary for maintenance of the gland, or I medium containing prolactin, aldosterone and hydrocortisone (IPAH medium) to induce lobuloalveolar development. At 3 and 7 days after exposure to 10 muM N-hydroxy-PhIP, mutant frequency was upwards of 9-fold higher in glands incubated in IPAH medium than in I medium (15.2 +/- 1.9 and 1.6 +/- 0.7x10(-3), respectively, 3 day time point). PhIP-DNA adduct levels were 1.7-fold higher in glands cultivated in IPAH medium than in I medium immediately after exposure to 10 muM N-hydroxy-PhIP. A statistically significant reduction in PhIP-DNA adduct levels occurred with time in glands cultivated in IPAH medium but not I medium (one-way analysis of variance, P < 0.05). By 7 days after exposure, PhIP-DNA adduct levels were similar in glands cultured in I and IPAH medium (3.2 +/- 0.2 and 2.8 +/- 0.29 adducts/10(7) nucleotides, respectively). DNA synthesis as measured by [H-3]thymidine labeling was &SIM;2-fold higher in glands cultured in IPAH medium than in I medium. The higher mutant frequency in glands cultivated in IPAH medium versus I medium appeared to be due to a combination of higher initial PhIP-DNA adduct levels and a greater fixation of mutations that occurred at higher proliferation rates. The findings indicate that mammotrophic hormones influence the mutagenicity of PhIP in the mammary gland in vitro and emphasize the importance of hormonal milieu on carcinogen-DNA adduct-induced mutations in this organ. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 3C28,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA. NR 39 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2003 VL 18 IS 1 BP 7 EP 12 DI 10.1093/mutage/18.1.7 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 626FB UT WOS:000179860700002 PM 12473729 ER PT S AU Miagkov, A Lobito, AA Yang, BZ Lopes, MF Adams, RN Palardy, GR Johnson, MM McFarland, HI Lenardo, MJ Drachman, DB AF Miagkov, A Lobito, AA Yang, BZ Lopes, MF Adams, RN Palardy, GR Johnson, MM McFarland, HI Lenardo, MJ Drachman, DB BE Agius, MA Richman, DP Fairclough, RH Maselli, RA TI Production and characterization of a T cell receptor transgenic mouse recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor SO MYASTHENIA GRAVIS AND RELATED DISORDERS: BIOMCHEMICAL BASIS FOR DISEASE OF THE NEUROMUSCULAR JUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Conference on Myasthenia Gravis and Related Disorders CY MAY, 2002 CL KEY BISCAYNE, FLORIDA SP New York Acad Sci, Myasthenia Gravis Fdn Amer Inc DE transgenic mice; immunodominant epitope; T cells; TAChR ID AUTOIMMUNE MYASTHENIA-GRAVIS; RESPONSES C1 Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21287 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Miagkov, A (reprint author), Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21287 USA. RI lopes, marcela/E-2201-2012; McFarland, Hugh/K-1503-2016 OI lopes, marcela/0000-0002-4508-0505; McFarland, Hugh/0000-0002-3322-038X NR 6 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-396-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 998 BP 379 EP 383 DI 10.1196/annals.1254.045 PG 5 WC Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BX68C UT WOS:000186107400044 PM 14592900 ER PT B AU Murphy, E Tong, HY Steenbergen, C AF Murphy, E Tong, HY Steenbergen, C BE Dhalla, NS Takeda, N Singh, M Lukas, A TI A role for the phosphatidylinositol-3-kinase pathway in preconditioning SO MYOCARDIAL ISCHEMIA AND PRECONDITIONING SE PROGRESS IN EXPERIMENTAL CARDIOLOGY LA English DT Proceedings Paper CT 17th World Heart Congress CY JUL 06-11, 2001 CL WINNIPEG, CANADA SP Int Soc Heart Res, Govt Canada, Dept Western Diversificat, Govt Manitoba, Dept Ind Trade & Mines Hlth, Post-Secondary Educ, Culture, Heritage Tourism, Merck Frosst Canada Ltd, Mitsubishi-Tokyo Pharmaceut Inc, ATL Canada, Beckman Coulter Canada Inc, Canadian Cardiovasc Soc, Canadian Inst Hlth Res, Cardiovasc Solut Inc, Dairy Farmers Canada, DeFehr Fdn, Univ Western Ontario, Fac Hlth Sci,, Heart & Stroke Fdn Manitoba, Inst Biodiagnost, Natl Res Council Canada, Japanese Working Grp Cardiac Struct & Metabolism, Manitoba Hydro, Merck KGaA, Pulsus Grp Inc, St Boniface Gen Hosp Res Ctr, Wawanesa Mutual Insurance Co, World Heart Corp DE preconditioning; phosphatidylinositol-3-kinase; glycogen synthase kinase; apoptosis; cardioprotection ID PROTEIN-KINASE-C; GROWTH-FACTOR-I; CONSCIOUS RABBITS; NITRIC-OXIDE; CELL-SURVIVAL; INDUCED CARDIOPROTECTION; ADENOSINE RECEPTORS; SENSITIVE MECHANISM; INDUCED APOPTOSIS; CARDIAC MYOCYTES AB Preconditioning has been shown to reduce cell death, although the mechanism responsible is still unclear. Activation of phosphatidylinositol-3-kinase (PI3K) has been shown to be cardioprotective. This paper will review the data suggesting a role for the PI3K pathways in cardioprotection and preconditioning. The PI3K pathway is activated by preconditioning and inhibition of PI3K blocks the protective effects of preconditioning. Thus, enhanced cell survival via activation of PI3K appears to be important in preconditioning. C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Murphy, E (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov NR 51 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBLISHERS PI NORWELL PA 101 PHILIP DRIVE, ASSINIPPI PARK, NORWELL, MA 02061 USA BN 1-4020-7195-7 J9 PROG EXP CARDIOL PY 2003 VL 6 BP 275 EP 282 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BW89Y UT WOS:000183540700019 ER PT S AU Mahaney, JE Albers, RW Kutchai, H Froehlich, JP AF Mahaney, JE Albers, RW Kutchai, H Froehlich, JP BE Jorgensen, PL Karlish, SJD Maunsbach, AB TI Phospholamban inhibits Ca2+ pump oligomerization and intersubunit free energy exchange leading to activation of cardiac muscle SERCA2a SO NA,K-ATPASE AND RELATED CATION PUMPS: STRUCTURE, FUNCTION, AND REGULATORY MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Conference on Na,K-ATPase and Related Cation Pumps CY AUG 08-14, 2002 CL ELSINORE, DENMARK DE cardiac muscle sarcoplasmic reticulum; phospholamban; SERCA2a; oligomerization; free energy exchange ID SARCOPLASMIC-RETICULUM; CALCIUM-PUMP C1 W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Mahaney, JE (reprint author), W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA. NR 6 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-401-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 986 BP 338 EP 340 PG 3 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BW85L UT WOS:000183407000079 PM 12763844 ER PT S AU Knepper, MA Kim, GH Masilamani, S AF Knepper, MA Kim, GH Masilamani, S BE Jorgensen, PL Karlish, SJD Maunsbach, AB TI Renal tubule sodium transporter abundance profiling in rat kidney - Response to aldosterone and variations in NaCl intake SO NA,K-ATPASE AND RELATED CATION PUMPS: STRUCTURE, FUNCTION, AND REGULATORY MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Conference on Na,K-ATPase and Related Cation Pumps CY AUG 08-14, 2002 CL ELSINORE, DENMARK DE hypertension; aldosterone; vasopressin; ENaC ID CL COTRANSPORTER; ENAC; PROTEOMICS; CHANNELS; SUBUNIT; CELLS; SGK AB Based on extensive physiological study of sodium transport mechanisms along the renal tubule, complementary DNAs for all of the major transporters and channels responsible for renal tubular sodium reabsorption have been cloned over the past decade. There is now a comprehensive set of cDNA and antibody probes that can he used to investigate physiological mechanisms on a molecular level. Using rabbit polyclonal antibodies to all of the major renal Na transport proteins, we have developed profiling methods allowing comprehensive, integrated analysis of sodium transporter protein abundance changes along the renal tubule in response to physiological and pathophysiological perturbations. Here, we review some of our recent findings with this approach, focusing on renal responses to aldosterone and to variations in NaCl intake. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Hallym Univ, Hangang Sacred Heart Hosp, Dept Internal Med, Seoul, South Korea. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. OI Kim, Gheun-Ho/0000-0002-8445-9892 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282-KE] NR 17 TC 23 Z9 23 U1 2 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-401-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 986 BP 562 EP 569 PG 8 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BW85L UT WOS:000183407000125 PM 12763890 ER PT S AU Wang, SQ Cheng, H Myers, AC Canning, BJ Xu, KY AF Wang, SQ Cheng, H Myers, AC Canning, BJ Xu, KY BE Jorgensen, PL Karlish, SJD Maunsbach, AB TI Positive inotropic effect induced by sequence-specific Na+,K+-ATPase antibody in intact cardiac myocytes SO NA,K-ATPASE AND RELATED CATION PUMPS: STRUCTURE, FUNCTION, AND REGULATORY MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Conference on Na,K-ATPase and Related Cation Pumps CY AUG 08-14, 2002 CL ELSINORE, DENMARK DE Na+,K+-ATPase; site-specific antibody; cardiac contraction ID (NA++K+)-ATPASE; SITE C1 Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21218 USA. NIA, Lab Cardiovasc Sci, Baltimore, MD 21224 USA. Peking Univ, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21224 USA. RP Xu, KY (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21218 USA. FU NHLBI NIH HHS [HL48198, HL52175] NR 2 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-401-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 986 BP 630 EP 632 PG 3 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BW85L UT WOS:000183407000140 PM 12763905 ER PT J AU Margolis, L AF Margolis, L TI Cytokines - strategic weapons in germ warfare? SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID GB-VIRUS-C; FUNCTIONAL EXPRESSION; LYMPHOID-TISSUE; T-CELLS; REPLICATION; INFECTION; HIV-1; CHEMOKINES; MIP-1-ALPHA; SUPPRESSION C1 NICHHD, Sect Intercellular Interact, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NICHHD, NASA NIH, Ctr 3 Dimens Tissue Culture, NIH, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), NICHHD, Sect Intercellular Interact, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 23 TC 18 Z9 18 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2003 VL 21 IS 1 BP 15 EP 16 DI 10.1038/nbt0103-15 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 632DV UT WOS:000180209200009 PM 12511900 ER PT J AU Liotta, LA Kohn, EC AF Liotta, LA Kohn, EC TI Cancer's deadly signature SO NATURE GENETICS LA English DT Editorial Material ID METASTASIS; TUMOR AB Theories of cancer biology have long held that the metastatic process originates with rare cells within the primary tumor. A new study using expression array analysis has identified a molecular signature of metastatic potential within the bulk of the primary tumor. This suggests that the majority of tumor cells have the potential to metastasize and presents exciting clinical and therapeutic applications. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 44 Z9 47 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2003 VL 33 IS 1 BP 10 EP 11 DI 10.1038/nb0103-10 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 630XH UT WOS:000180136100006 PM 12509774 ER PT J AU Pollock, PM Harper, UL Hansen, KS Yudt, LM Stark, M Robbins, CM Moses, TY Hostetter, G Wagner, U Kakareka, J Salem, G Pohida, T Heenan, P Duray, P Kallioniemi, O Hayward, NK Trent, JM Meltzer, PS AF Pollock, PM Harper, UL Hansen, KS Yudt, LM Stark, M Robbins, CM Moses, TY Hostetter, G Wagner, U Kakareka, J Salem, G Pohida, T Heenan, P Duray, P Kallioniemi, O Hayward, NK Trent, JM Meltzer, PS TI High frequency of BRAF mutations in nevi SO NATURE GENETICS LA English DT Article AB To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Queensland Inst Med Res, Canc & Cell Biol Div, Herston, Qld 4006, Australia. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Western Australia, Queen Elizabeth II Med Ctr, Dept Pathol, Nedlands, WA 6009, Australia. NCI, NIH, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-5111-2011; Stark, Mitchell/E-3542-2010; Kallioniemi, Olli/H-4738-2012; hayward, nicholas/C-1367-2015; OI Kallioniemi, Olli/0000-0002-3231-0332; Stark, Mitchell/0000-0002-4510-2161; Kallioniemi, Olli/0000-0002-3231-0332; hayward, nicholas/0000-0003-4760-1033; Kakareka, John/0000-0003-0072-0035 NR 6 TC 925 Z9 940 U1 2 U2 37 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2003 VL 33 IS 1 BP 19 EP 20 DI 10.1038/ng1054 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 630XH UT WOS:000180136100010 PM 12447372 ER PT J AU Anderson, HA Maylock, CA Williams, JA Paweletz, CP Shu, HJ Shacter, E AF Anderson, HA Maylock, CA Williams, JA Paweletz, CP Shu, HJ Shacter, E TI Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells SO NATURE IMMUNOLOGY LA English DT Article ID MACROPHAGE RECOGNITION; VITRONECTIN RECEPTOR; BLOOD-COAGULATION; GENERAL FEATURE; CLEARANCE; GAS6; LYMPHOCYTES; EXPOSURE; ANTIBODIES; INHIBITION AB Rapid phagocytosis of apoptotic cells is thought to limit the development of inflammation and autoimmune disease. Serum enhances macrophage phagocytosis of apoptotic cells. Here we identified protein S as the factor responsible for serum-stimulated phagocytosis of apoptotic cells. Protein S is best known for its anti-thrombotic activity, serving as a cofactor for protein C. Purified protein S was equivalent to serum in its ability to stimulate macrophage phagocytosis of apoptotic lymphoma cells, and immunodepletion of protein S eliminated the prophagocytic activity of serum. Protein S acted by binding to phosphatidylserine expressed on the apoptotic cell surface. Protein S is thus a multifunctional protein that can facilitate clearance of early apoptotic cells in addition to regulating blood coagulation. C1 US FDA, Biochem Lab, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20815 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Dept Pharmacol, SW Med Ctr, Dallas, TX 75390 USA. RP Shacter, E (reprint author), US FDA, Biochem Lab, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NR 42 TC 213 Z9 220 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2003 VL 4 IS 1 BP 87 EP 91 DI 10.1038/ni871 PG 5 WC Immunology SC Immunology GA 629MG UT WOS:000180053000019 PM 12447359 ER PT J AU Carlezon, WA Wise, RA AF Carlezon, WA Wise, RA TI Unmet expectations: The brain minds SO NATURE MEDICINE LA English DT Editorial Material ID NUCLEUS-ACCUMBENS; COCAINE; EXPRESSION; ADDICTION C1 Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Carlezon, WA (reprint author), Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RI Wise, Roy/A-6465-2012 NR 11 TC 5 Z9 6 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2003 VL 9 IS 1 BP 15 EP 16 DI 10.1038/nm0103-15 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 632EC UT WOS:000180209900011 PM 12514711 ER PT J AU Leitner, WW Hwang, LN deVeer, MJ Zhou, AM Silverman, RH Williams, BRG Dubensky, TW Ying, H Restifo, NP AF Leitner, WW Hwang, LN deVeer, MJ Zhou, AM Silverman, RH Williams, BRG Dubensky, TW Ying, H Restifo, NP TI Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways SO NATURE MEDICINE LA English DT Article ID DOUBLE-STRANDED-RNA; ANTIGEN-PRESENTING CELLS; SEMLIKI-FOREST-VIRUS; NF-KAPPA-B; SINDBIS-VIRUS; DENDRITIC CELLS; IMMUNE-RESPONSES; INTERFERON ACTION; REPLICON VECTORS; GENE-EXPRESSION AB Cancer vaccines targeting 'self' antigens that are expressed at consistently high levels by tumor cells are potentially useful in immunotherapy, but immunological tolerance may block their function. Here, we describe a novel, naked DNA vaccine encoding an alphavirus replicon (self-replicating mRNA) and the self/tumor antigen tyrosinase-related protein-1. Unlike conventional DNA vaccines, this vaccine can break tolerance and provide immunity to melanoma. The vaccine mediates production of double-stranded RNA, as evidenced by the autophosphorylation of dsRNA-dependent protein kinase R (PKR). Double-stranded RNA is critical to vaccine function because both the immunogenicity and the anti-tumor activity of the vaccine are blocked in mice deficient for the RNase L enzyme, a key component of the 2',5-linked oligoadenylate synthetase antiviral pathway involved in double-stranded RNA recognition. This study shows for the first time that alphaviral replicon-encoding DNA vaccines activate innate immune pathways known to drive antiviral immune responses, and points the way to strategies for improving the efficacy of immunization with naked DNA. C1 NCI, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Canc Biol, Cleveland, OH 44195 USA. Cleveland State Univ, Dept Chem, Clin Chem Program, Cleveland, OH 44115 USA. Chiron Corp, Ctr Gene Therapy, Emeryville, CA 94608 USA. RP Leitner, WW (reprint author), NCI, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Leitner, Wolfgang/F-5741-2011; Williams, Bryan/A-5021-2009; OI Leitner, Wolfgang/0000-0003-3125-5922; Williams, Bryan/0000-0002-4969-1151; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [CA44059, R01 CA044059]; NIAID NIH HHS [R01 AI034039, R01-AI34039] NR 46 TC 200 Z9 229 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2003 VL 9 IS 1 BP 33 EP 39 DI 10.1038/nm813 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 632EC UT WOS:000180209900019 PM 12496961 ER PT J AU De Rosa, SC Brenchley, JM Roederer, M AF De Rosa, Stephen C. Brenchley, Jason M. Roederer, Mario TI Beyond six colors: A new era in flow cytometry SO NATURE MEDICINE LA English DT Article ID ANTIGEN-BINDING CELLS; RESPONSES IN-VIVO; CD8(+) T-CELLS; 2 SUBSETS; MEMORY; LYMPHOCYTES; IDENTIFICATION; FLUORESCENCE; SEPARATION; AFFINITY AB More than 100 functionally distinct populations of lymphocytes can be identified in the peripheral blood of humans; each of these cell types undoubtedly has a unique role in the organization and effectiveness of an immune response. To distinguish specifically among these cells, however, it is necessary to measure simultaneously at least six to eight different T-cell surface antigens; additional functional correlations require even greater detection capability. For this purpose, flow cytometers capable of independently detecting as many as 12 different molecules now exist. Here we review the history and applications of this technology and discuss future directions. C1 [De Rosa, Stephen C.; Brenchley, Jason M.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM roederer@nih.gov NR 28 TC 125 Z9 127 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2003 VL 9 IS 1 BP 112 EP 117 DI 10.1038/nm0103-112 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA V27VJ UT WOS:000208640400005 PM 12514723 ER PT J AU Steeg, PS AF Steeg, PS TI Metastasis suppressors alter the signal transduction of cancer cells SO NATURE REVIEWS CANCER LA English DT Review ID MAMMARY-ADENOCARCINOMA CELLS; PROTEIN-COUPLED RECEPTOR; EPIDERMAL GROWTH-FACTOR; RESPONSE MEDIATOR PROTEIN-1; KINASE ALPHA-ISOFORM; IN-VIVO INVASIVENESS; BREAST-CANCER; EGF RECEPTOR; PROSTATE-CANCER; DIPHOSPHATE KINASE AB Tumour metastasis is a significant contributor to death in cancer patients. Eight metastasis-suppressor genes that reduce the metastatic propensity of a cancer cell line in vivo without affecting its tumorigenicity have been identified. These affect important signal-transduction pathways, including mitogen-activated protein kinases, RHO, RAC and G-protein-coupled and tyrosine-kinase receptors. So how might we use this knowledge to improve the treatment of patients with cancer?. C1 NCI, Womens Canc Sect, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NR 110 TC 330 Z9 345 U1 3 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2003 VL 3 IS 1 BP 55 EP 63 DI 10.1038/nrc967 PG 9 WC Oncology SC Oncology GA 636HK UT WOS:000180448400015 PM 12509767 ER PT J AU Mulshine, JL AF Mulshine, JL TI Screening for lung cancer: in pursuit of pre-metastatic disease SO NATURE REVIEWS CANCER LA English DT Editorial Material ID COMPUTER-AIDED DIAGNOSIS; SMALL PULMONARY NODULES; HELICAL CT IMAGES; SMOKING CESSATION; CONTROLLED TRIALS; MORTALITY TRENDS; PROSTATE-CANCER; ACTION PROJECT; RETINOIC ACID; UNITED-STATES AB One reason for the high death rate of lung cancer is that tumours are not usually detected until the disease is at a late stage, at which point the cancer is non-curable. Spiral computerized tomography is a highly sensitive imaging method that could be used to screen high-risk populations, such as current or former smokers, for early-stage tumours. Trials to validate this tool are just underway, but beyond the imaging tools, population-based care of pre-metastatic lung cancer requires considerable evolution in clinical management approaches. More sensitive imaging tools might also provide a window into earlier biology, enabling the molecular dynamics of lung cancer progression to be elucidated. C1 NCI, Intervent Sect, Cell & Canc Biol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Cell & Canc Biol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 113 TC 37 Z9 39 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2003 VL 3 IS 1 BP 65 EP 73 DI 10.1038/nrc972 PG 9 WC Oncology SC Oncology GA 636HK UT WOS:000180448400016 PM 12509768 ER PT J AU Plotz, PH AF Plotz, PH TI The autoantibody repertoire: searching for order SO NATURE REVIEWS IMMUNOLOGY LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSFER-RNA-SYNTHETASE; AUTOIMMUNE-DISEASE; APOPTOTIC CELLS; DENDRITIC CELLS; IMMUNE-SYSTEM; MICE; INDUCTION; RECOGNITION; ANTIBODIES AB The spontaneously occurring autoantibodies that are associated with human diseases bear the hallmarks of a typical immune response. The repertoire of autoantibodies is surprisingly limited, however, and is the same in both humans and mice. Neither molecular mimicry nor immune dysregulation accounts for this unexpectedly narrow focus of specificities. Experimental data on the properties of the target autoantigens - such as their structure, catabolism, exposure to the immune system after cell death and recently described immunostimulatory effects on immature dendritic cells - indicate that these properties, in conjunction with the tissue microenvironment, help to select the autoantibody repertoire. C1 NIAMSD, Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Plotz, PH (reprint author), NIAMSD, Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 47 TC 117 Z9 120 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2003 VL 3 IS 1 BP 73 EP 78 DI 10.1038/nri976 PG 6 WC Immunology SC Immunology GA 637HG UT WOS:000180505200023 PM 12511877 ER PT J AU Lippincott-Schwartz, J Altan-Bonnet, N Patterson, GH AF Lippincott-Schwartz, Jennifer Altan-Bonnet, Nihal Patterson, George H. TI Photobleaching and photoactivation: following protein dynamics in living cells SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review AB Cell biology is being transformed by the use of fluorescent proteins as fusion tags to track protein behaviour in living cells. Here, we discuss the techniques of photobleaching and photoactivation, which can reveal the location and movement of proteins. Widespread applications of these fluorescent-based methods are revealing new aspects of protein dynamics and the biological processes that they regulate. C1 [Lippincott-Schwartz, Jennifer; Altan-Bonnet, Nihal; Patterson, George H.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, NIH, Bldg 18T-Room 101, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov NR 87 TC 0 Z9 0 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PY 2003 SU S BP S7 EP S14 DI 10.1038/ncb1032 PG 9 WC Cell Biology SC Cell Biology GA V54VU UT WOS:000203707000003 ER PT J AU Neale, EA AF Neale, EA TI Moving across membranes SO NATURE STRUCTURAL BIOLOGY LA English DT Editorial Material ID PLANAR PHOSPHOLIPID-BILAYERS; DIPHTHERIA-TOXIN; BOTULINUM NEUROTOXIN; CATALYTIC DOMAIN; T-DOMAIN; TRANSLOCATION; FRAGMENT; BINDING C1 NICHHD, Sect Cell Biol, NIH, Bethesda, MD 20892 USA. RP Neale, EA (reprint author), NICHHD, Sect Cell Biol, NIH, Bethesda, MD 20892 USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JAN PY 2003 VL 10 IS 1 BP 2 EP 3 DI 10.1038/nsb0103-2 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 632GT UT WOS:000180216100002 PM 12490883 ER PT J AU Oz, M Tchugunova, Y Dinc, M AF Oz, M Tchugunova, Y Dinc, M TI Inhibition of cromakalim-activated K+ current by ethanol in follicle-enclosed Xenopus oocytes SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE cromakalim; ethanol; K-ATP channels; Xenopus oocytes ID ION CHANNELS; INDUCED CONTRACTION; OPENERS; CA2+; MECHANISM; INJECTION; ARTERIES; ALCOHOLS; CALCIUM AB Ethanol has been reported to modulate arterial dilation and insulin secretion. ATP-inhibited K+ channels (K-ATP) are reported to have regulatory roles during these events. In the present study, the effect of ethanol on K+ currents activated by the K-ATP channel opener cromakalim was investigated in follicular cells of Xenopus oocytes. The results indicate that ethanol in the concentration range of 10-300 mM (approximately 0.06%-2% v/v) reversibly inhibits the cromakalim-induced K+ currents. The 50% of maximal ethanol effect was obtained at 53 mM. Inhibition of cromakalim-activated K+ current by ethanol was non-competitive. In oocytes treated with the Ca2+-chelator BAPTA, inhibition of cromakalim-induced K+ currents by ethanol was not altered, suggesting that Ca2+-activated second messenger pathways were not involved in the actions of ethanol. Similarly, currents activated by 8-Br-cAMP were also inhibited by ethanol, but the ethanol inhibition of 8-Br-cAMP-activated currents was significantly less than inhibition of cromakalim-activated currents by ethanol. These results indicate that cromakalim-activated K+ currents in follicular cells of Xenopus oocytes were modulated by ethanol. C1 NIDA, IRP, Cellular Neurobiol Branch, Baltimore, MD 21224 USA. Oncol Hosp, Dept Pulm Dis, TR-06947 Ankara, Turkey. RP Oz, M (reprint author), NIDA, IRP, Cellular Neurobiol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Oz, Murat/E-2148-2012 NR 27 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JAN PY 2003 VL 367 IS 1 BP 80 EP 85 DI 10.1007/s00210-002-0643-x PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 646BD UT WOS:000181014200011 PM 12616345 ER PT J AU Yao, RS Wang, Y Lubet, RA You, M AF Yao, RS Wang, Y Lubet, RA You, M TI Differential gene expression in chemically induced mouse lung adenomas SO NEOPLASIA LA English DT Article DE lung adenomas; CCLS; expression profile; differential changes; cancer genes ID ENVIRONMENTAL TOBACCO-SMOKE; SIGNAL-REGULATED KINASE; VEIN ENDOTHELIAL-CELLS; IMMEDIATE-EARLY GENE; CARBONIC-ANHYDRASE; BINDING PROTEIN; CANCER CELLS; RAS; TUMORS; ACTIVATION AB Because of similarities in histopathology and tumor progression stages between mouse and human lung adenocarcinomas, the mouse lung tumor model with lung adenomas as the endpoint has been used extensively to evaluate the efficacy of putative lung cancer chemopreventive agents. In this study, a competitive cDNA library screening (CCLS) was employed to determine changes in the expression of mRNA in chemically induced lung adenomas compared with paired normal lung tissues. A total of 2555 clones having altered expression in tumors were observed following competitive hybridization between normal lung and lung adenomas after primary screening of over 160,000 clones from a mouse lung cDNA library. Among the 755 clones confirmed by dot blot hybridization, 240 clones were underexpressed, whereas 515 clones were overexpressed in tumors. Sixty-five clones with the most frequently altered expression in six individual tumors were confirmed by semiquantitative RT-PCR. When examining the 58 known genes, 39 clones had increased expression and 19 had decreased expression, whereas the 7 novel genes showed overexpression. A high percentage (>60%) of overexpressed or underexpressed genes was observed in at least two or three of the lesions. Reproducibly overexpressed genes included ERK-1, JAK-1, surfactant proteins A, B, and C, NFAT1, alpha-1 protease inhibitor, helix-loop-helix ubiquitous kinase (CHUK), alpha-adaptin, alpha-1 PI2, thioether S-methyltransferase, and CYP2C40. Reproducibly underexpressed genes included paroxanase, ALDH II, CC10, von Ebner salivary gland protein, and alpha- and beta-globin. In addition, CCLS identified several novel genes or genes not previously associated with lung carcinogenesis, including a hypothetical protein (FLJ1 1240) and a guanine nucleotide exchange factor homologue. This study shows the efficacy of this methodology for identifying genes with altered expression. These genes may prove to be helpful in our understanding of the genetic basis of lung carcinogenesis and in developing biomarkers for lung cancer chemoprevention studies in mice. C1 Ohio State Univ, James Canc Ctr, Sch Publ Hlth, Columbus, OH 43210 USA. Ohio State Univ, James Canc Ctr, Div Human Canc Genet, Columbus, OH 43210 USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP You, M (reprint author), Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Med Res Facil 514, 420 W 12th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [CA78797, CA58554, CN05113, P30 CA016058, R01 CA058554] NR 46 TC 19 Z9 21 U1 2 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN-FEB PY 2003 VL 5 IS 1 BP 41 EP 52 PG 12 WC Oncology SC Oncology GA 640DQ UT WOS:000180672600006 PM 12659669 ER PT J AU Jeon, US Joo, KW Na, KY Kim, YS Lee, JS Kim, J Kim, GH Nielsen, S Knepper, MA Han, JS AF Jeon, US Joo, KW Na, KY Kim, YS Lee, JS Kim, J Kim, GH Nielsen, S Knepper, MA Han, JS TI Oxytocin induces apical and basolateral redistribution of aquaporin-2 in rat kidney SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE aquaporin-2; oxytocin; vasopressin-2 receptor; redistribution; basolateral; kidney ID VASOPRESSIN-INDUCED ANTIDIURESIS; MEDULLARY COLLECTING DUCT; WATER CHANNEL EXPRESSION; INDUCED DOWN-REGULATION; RENAL AQUAPORINS; EPITHELIAL-CELLS; PLASMA-MEMBRANE; PERMEABILITY; RECEPTOR; TUBULE AB The aquaporin-2 (AQP2) water channel is mainly located in the apical plasma membrane of collecting duct epithelial cells, but there has been some evidence of a moderate amount of basolateral localization of AQP2 at least in the inner medullary collecting duct (IMCD). Previous in vitro microperfusion studies showed that oxytocin has an antidiuretic action, most likely mediated by the vasopressin V-2 receptor (V2R) in rat IMCD. By using immunohistochemistry in kidneys from male Sprague-Dawley rats, we observed acute effects of oxytocin on AQP2 localization which were prevented by a V2R antagonist. After intraperitoneal administration of oxytocin (10 U), immunohistochemistry of IMCD revealed that AQP2 was shifted from diffuse cytoplasmic localization in controls to the apical and basolateral membrane domains in oxytocin-treated rats. This pattern of AQP2 redistribution was noted in connecting tubule, cortical collecting duct and outer medullary collecting duct as well as in IMCD, although the tendency to basolateral localization was somewhat less. The pretreatment using a V2R antagonist blocked redistribution of AQP2 in response to oxytocin. We conclude that oxytocin induces a V2R-mediated redistribution of AQP2-containing cytoplasmic vesicles to both apical and basolateral plasma membrane domains in rat kidney. Oxytocin may be one of the factors that accounts for vasopressin-independent AQP2 targeting in the kidney. Copyright (C) 2003 S. Karger AG, Basel. C1 Seoul Natl Univ, Seoul Natl Univ Hosp, Clin Res Inst, Dept Internal Med, Seoul 110744, South Korea. Gyeongsang Natl Univ, Dept Internal Med, Chinju, South Korea. Gachon Med Sch, Dept Internal Med, Inchon, South Korea. Catholic Univ, Dept Anat, Seoul, South Korea. Hallym Univ, Hangang Sacred Heart Hosp, Dept Internal Med, Seoul, South Korea. Univ Aarhus, Dept Cell Biol, Aarhus, Denmark. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Han, JS (reprint author), Seoul Natl Univ, Seoul Natl Univ Hosp, Clin Res Inst, Dept Internal Med, 28 Yongun Dong, Seoul 110744, South Korea. RI Na, Ki Young/J-5456-2012; Han, Jin-Suk/J-5711-2012; Joo, Kwon Wook/J-5675-2012 FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 32 TC 24 Z9 25 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PD JAN PY 2003 VL 93 IS 1 BP E36 EP E45 DI 10.1159/000066651 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 742LW UT WOS:000186519900007 PM 12411748 ER PT J AU Teipel, SJ Bayer, W Alexander, GE Bokde, ALW Zebuhr, Y Teichberg, D Muller-Spahn, F Schapiro, MB Moller, HJ Rapoport, SI Hampel, H AF Teipel, SJ Bayer, W Alexander, GE Bokde, ALW Zebuhr, Y Teichberg, D Muller-Spahn, F Schapiro, MB Moller, HJ Rapoport, SI Hampel, H TI Regional pattern of hippocampus and corpus callosum atrophy in Alzheimer's disease in relation to dementia severity: evidence for early neocortical degeneration SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; disease progression; clinical stages; neurodegeneration; brain atrophy; hippocampus; amygdala; corpus callosum; allocortex; neocortex; magnetic resonance imaging; ROC ID OPERATING CHARACTERISTIC CURVES; POSITRON EMISSION TOMOGRAPHY; VOXEL-BASED MORPHOMETRY; WHITE-MATTER PATHOLOGY; GLUCOSE-METABOLISM; HYPERINTENSITIES; PROGRESSION; VALIDATION; IMPAIRMENT; INDICATOR AB We used volumetric MRI and analysis of areas under receiver operating characteristic (ROC) curves to directly compare the extent of hippocampus-amygdala formation (HAF) and corpus callosum atrophy in patients with Alzheimer's disease (AD) in different clinical stages of dementia. Based on neuropathological studies, we hypothesized that HAF atrophy, representing allocortical neuronal degeneration, would precede atrophy of corpus callosum, representing loss of neocortical association neurons, in early AD. HAF and corpus callosum sizes were significantly reduced in 27 AD patients (37% and 16%, respectively) compared to 28 healthy controls. In mildly- and moderately-demented AD patients, the ROC derived index of atrophy was greater for HAF volume than for total corpus callosum area. The index of atrophy of posterior corpus callosum was not significantly different from HAF at mild, moderate or severe stages of dementia. In conclusion, these findings suggest a characteristic regional pattern of allocortical and neocortical neurodegeneraton in AD. Our data indicate that neuronal loss in parietotemporal cortex (represented by atrophy of corpus callosum splenium) may occur simultaneously with allocortical neurodegeneration in mild AD. Moreover, ROC analysis may provide a statistical framework to determine atrophy patterns of different brain structures in neurodegenerative diseases in vivo. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Munich, Dept Psychiat, Dementia & Neuroimaging Sect, D-80336 Munich, Germany. Arizona State Univ, Arizona Alzheimers Dis Res Ctr, MRI Morphol Core, Tempe, AZ USA. Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. Univ Basel, Dept Psychiat, Basel, Switzerland. Childrens Hosp, Med Ctr, Dept Pediat Neurol, Cincinnati, OH 45229 USA. RP Teipel, SJ (reprint author), Univ Munich, Dept Psychiat, Dementia & Neuroimaging Sect, Nussbaumstr 7, D-80336 Munich, Germany. NR 51 TC 67 Z9 70 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN-FEB PY 2003 VL 24 IS 1 BP 85 EP 94 AR PII S0197-4580(02)00044-1 DI 10.1016/S0197-4580(02)00044-1 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 636LT UT WOS:000180458000008 PM 12493554 ER PT J AU Umhau, JC Petrulis, SG Diaz, R Rawlings, R George, DT AF Umhau, JC Petrulis, SG Diaz, R Rawlings, R George, DT TI Blood glucose is correlated with cerebrospinal fluid neurotransmitter metabolites SO NEUROENDOCRINOLOGY LA English DT Article DE glucose; cerebrospinal fluid; 3-methoxy-4-hydroxyphenylglycol; homovanillic acid; 5-hydroxyindoleacetic acid; catecholamines; serotonin; clinical neuroendocrinology ID VENTROMEDIAL HYPOTHALAMUS; NEURONAL-ACTIVITY; DIABETES-MELLITUS; NORADRENERGIC NEURONS; MONOAMINE METABOLITES; TARDIVE-DYSKINESIA; ANESTHETIZED RATS; INSULIN LEVELS; ACID LEVELS; BRAIN AB Medications which influence monoaminergic neurotransmission can also have an effect on glucose regulation. In order to better understand the role of central monoaminergic neurotransmission in blood glucose homeostasis, we explored the relation between blood glucose and cerebrospinal fluid metabolite concentrations of monoaminergic neurotransmitters. Under stringently controlled resting conditions, we measured fasting blood glucose and performed lumbar punctures on 41 healthy participants. Peripheral blood glucose concentrations were significantly correlated with the cerebrospinal fluid concentrations of the dopamine metabolite, homovanillic acid and the noradrenaline metabolite, 3-methoxy-4-hydroxyphenylglycol. These correlations may represent a homeostatic relation between brain neurotransmitter activity and blood glucose. Copyright (C) 2003 S. Karger AG, Basel. C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Umhau, JC (reprint author), NIAAA, Clin Studies Lab, NIH, 10 Ctr Dr,MSC-1610,Bldg 10,Room 6S-204, Bethesda, MD 20892 USA. NR 47 TC 12 Z9 13 U1 3 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2003 VL 78 IS 6 BP 339 EP 343 DI 10.1159/000074887 PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 756EP UT WOS:000187453100007 PM 14688447 ER PT J AU Trojanowski, JQ Mattson, MP AF Trojanowski, JQ Mattson, MP TI Overview of protein aggregation in single, double, and triple neurodegenerative brain amyloidoses SO NEUROMOLECULAR MEDICINE LA English DT Editorial Material ID ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; DISORDERS; PREVENTION; DROSOPHILA; MECHANISM; TOXICITY; TAU C1 Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RI Mattson, Mark/F-6038-2012 NR 24 TC 28 Z9 29 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 4 IS 1-2 BP 1 EP 5 DI 10.1385/NMM:4:1-2:1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 736KU UT WOS:000186170600001 PM 14528048 ER PT J AU Mattson, MP Sherman, M AF Mattson, MP Sherman, M TI Perturbed signal transduction in neurodegenerative disorders involving aberrant protein aggregation SO NEUROMOLECULAR MEDICINE LA English DT Review ID AMYLOID-BETA-PEPTIDE; LIPID-PEROXIDATION PRODUCT; EXPANDED POLYGLUTAMINE PROTEIN; CORTICAL SYNAPTIC TERMINALS; INTRACELLULAR A-BETA; NF-KAPPA-B; ALZHEIMERS-DISEASE; HUNTINGTONS-DISEASE; HIPPOCAMPAL-NEURONS; ALPHA-SYNUCLEIN AB Aggregation of abnormal proteins, both inside and outside of cells, is a prominent feature of major neurodegenerative disorders, including Alzheimer's, Parkinson's, polyglutamine expansion, and prion diseases. Other articles in this special issue of NeuroMolecular Medicine describe the genetic and molecular factors that promote aberrant protein aggregation. In the present article, we consider how it is that pathogenic aggregation-prone proteins compromise signal transduction pathways that regulate neuronal plasticity and survival. In some cases the protein in question may have widespread and relatively nonspecific effects on signaling. For example, amyloid beta-peptide induces membrane-associated oxidative stress, which impairs the function of various receptors, ion channels and transporters, as well as downstream kinases and transcription factors. Other proteins, such as polyglutamine repeat proteins, may affect specific protein-protein interactions, including those involved in signaling pathways activated by neurotransmitters, neurotrophins, and steroid hormones. Synapses are particularly sensitive to abnormal protein aggregation and impaired synaptic signaling may trigger apoptosis and related cell death cascades. Impairment of signal transduction in protein aggregation disorders may be amenable to therapy as demonstrated by a recent study showing that dietary restriction can preserve synaptic function and protect neurons in a mouse model of Huntington's disease. Finally, emerging findings are revealing how activation of certain signaling pathways can suppress protein aggregation and/or the cytotoxicity resulting from the abnormal protein aggregation. A better understanding of how abnormal protein aggregation occurs and how it affects and is affected by specific signal transduction pathways, is leading to novel approaches for preventing and treating neurodegenerative disorders. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 213 TC 18 Z9 19 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 4 IS 1-2 BP 109 EP 131 DI 10.1385/NMM:4:1-2:109 PG 23 WC Neurosciences SC Neurosciences & Neurology GA 736KU UT WOS:000186170600009 PM 14528056 ER PT J AU Lee, LW Auyeung, WW Mattson, MP AF Lee, LW Auyeung, WW Mattson, MP TI Interactive effects of excitotoxic injury and dietary restriction on microgliosis and neurogenesis in the hippocampus of adult mice SO NEUROMOLECULAR MEDICINE LA English DT Article DE astrocytes; apoptosis; microglia; epilepsy; seizures; stem cells; proliferation ID AMYLOID BETA-PEPTIDE; GRANULE CELL NEUROGENESIS; RAT DENTATE GYRUS; STATUS EPILEPTICUS; NEUROTROPHIC FACTOR; STEM-CELLS; PRESENILIN-1 MUTATION; ENRICHED ENVIRONMENT; SUBVENTRICULAR ZONE; ALZHEIMERS-DISEASE AB Responses to neuronal degeneration are complex, involving activation of microglia, astrocytes, and synaptic remodeling. It has also been suggested that neuronal injury stimulates neurogenesis, the production of new neurons from neural stem cells. Because dietary restriction (DR) can increase hippocampal neurogenesis and promotes the survival of neurons following injury, we determined the effects of DR on the responses of neural stem cells, microglia, and astrocytes in the hippocampus to seizure-induced hippocampal damage. Mice on ad libitum or DR diets were given an intrahippocampal injection of kainate, administered the DNA precursor bromodeoxyuridine (BrdU) during a 5-d period, and euthanized 1 d or 3 wk later. Although kainate greatly increased the numbers of BrdU-Iabeled cells, it did not enhance neurogenesis and damaged neurons were not replaced. Instead, most BrdU-Iabeled cells were either proliferating microglia or neural progenitor cells that subsequently died. Microgliosis was transient and was strongly correlated with the amount of damage to CA3 neurons, whereas astrocytosis was delayed and not correlated with neuronal loss. Surprisingly, neurogenesis was not increased in response to seizure-induced damage, and although DR increased basal neurogenesis, it did not promote neurogenesis following brain injury. DR significantly decreased seizure-induced microgliosis, but did not affect astrocytosis. Our findings show that DR suppresses injury-induced microgliosis suggesting a contribution of a reduced microglial response to the neuroprotective effects of DR. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 60 TC 20 Z9 20 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 4 IS 3 BP 179 EP 195 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 760MM UT WOS:000187837700003 ER PT J AU Cookson, MR AF Cookson, MR TI Parkin's substrates and the pathways leading to neuronal damage SO NEUROMOLECULAR MEDICINE LA English DT Review DE Parkinson's disease; proteasome; ubiquitin; cell death; alpha-synuclein; tau; synphilin; cdc-rel1; Pael-r1 ID RECESSIVE JUVENILE PARKINSONISM; UBIQUITIN-PROTEIN LIGASE; ALPHA-SYNUCLEIN; MESSENGER-RNA; LEWY BODIES; HUMAN BRAIN; TAU GENE; DISEASE; MUTATIONS; ASSOCIATION AB Mutations in the Parkin gene are associated with Parkinson's disease (PD). The gene product has been shown to be an E3 protein-ubiquitin ligase, catalyzing the addition of ubiquitin to target proteins prior to their destruction via the proteasome. This activity is thus key in regulating the turnover of substrate proteins. A predictive hypothesis for how this results in PD is that the misregulation of proteasomal degradation of Parkin's substrates is deleterious to neurons. Several different laboratories have identified alternate candidate proteins. In this review, the likelihood of each of the proposed substrates for parkin being robust will be evaluated. The distribution and abundance of the proteins will be examined for clues as to which are the pathologically important substrates for parkin. The possibility that loss of regulation of turnover of one or more of these substrates contributes to the selective neurodegeneration seen in PD is also discussed. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. FU NINDS NIH HHS [P01-NS40256, R01-NS41816-01] NR 69 TC 41 Z9 44 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 3 IS 1 BP 1 EP 13 DI 10.1385/NMM:3:1:1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 655BL UT WOS:000181531400001 PM 12665672 ER PT J AU Nath, A Hall, E Tuzova, M Dobbs, M Jones, M Anderson, C Woodward, J Guo, ZH Fu, WM Kryscio, R Wekstein, D Smith, C Markesbery, WR Mattson, MP AF Nath, A Hall, E Tuzova, M Dobbs, M Jones, M Anderson, C Woodward, J Guo, ZH Fu, WM Kryscio, R Wekstein, D Smith, C Markesbery, WR Mattson, MP TI Autoantibodies to amyloid beta-peptide (A beta) are increased in Alzheimer's disease patients and A beta antibodies can enhance A beta neurotoxicity - Implications for disease pathogenesis and vaccine development SO NEUROMOLECULAR MEDICINE LA English DT Article DE apoptosis; hippocampal; immune; secretase; transgenic ID PRECURSOR PROTEIN; HIPPOCAMPAL-NEURONS; SENILE PLAQUES; MOUSE MODEL; IN-VITRO; MICE; PRESENILIN-1; IMMUNIZATION; PATHOLOGY; TAU AB Studies of amyloid precursor protein transgenic mice suggest that immune responses to amyloid beta peptide (Abeta) may be instrumental in the removal of plaques from the brain, but the initial clinical trial of an Abeta vaccine in patients with Alzheimer's disease (AD) was halted as the result of serious neurological complications in some patients. We now provide evidence that AD patients exhibit an enhanced immune response to Abeta and that, contrary to expectations, Abeta antibodies enhance the neurotoxic activity of the peptide. Serum titers to Abeta were significantly elevated in AD patients and Abeta antibodies were found in association with amyloid plaques in their brains, but there was no evidence of cell-mediated immune responses to Abeta in the patients. Abeta antibodies were detected in the serum of old APP mutant transgenic mice with plaque-like Abeta deposits, but not in the serum of younger transgenic or nontransgenic mice. Serum from APP mutant mice potentiated the neurotoxicity of Abeta. Our data suggest that a humoral immune response to Abeta in AD patients may promote neuronal degeneration, a process with important implications for the future of vaccine-based therapies for AD. C1 Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. Univ Kentucky, Dept Microbiol & Immunol, Lexington, KY 40536 USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RI Mattson, Mark/F-6038-2012 NR 35 TC 71 Z9 74 U1 2 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 3 IS 1 BP 29 EP 39 DI 10.1385/NMM:3:1:29 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 655BL UT WOS:000181531400003 PM 12665674 ER PT J AU Pak, K Chan, SL Mattson, MP AF Pak, K Chan, SL Mattson, MP TI Presenilin-1 mutation sensitizes oligodendrocytes to glutamate and amyloid toxicities, and exacerbates white matter damage and memory impairment in mice SO NEUROMOLECULAR MEDICINE LA English DT Article DE Alzheimer's disease; amyloid beta-peptide; apoptosis; axons; calcium; cognitive; excitotoxicity; white matter ID CUPRIZONE-INDUCED DEMYELINATION; ALZHEIMERS-DISEASE BRAIN; CENTRAL-NERVOUS-SYSTEM; CULTURED OLIGODENDROCYTES; PRECURSOR PROTEIN; CORTICAL-NEURONS; TRANSGENIC MICE; GROWTH-FACTOR; BETA-PEPTIDE; REMYELINATION AB Damage to white matter occurs in the brains of patients with Alzheimer's disease (AD), but it is not known if and how oligodendrocytes are affected in AD, nor whether white matter alterations contribute to the cognitive dysfunction in this disease. Mutations in the gene encoding presenilin-1 (PS1) cause some cases of early-onset inherited AD. These mutations may promote neuronal degeneration by increasing the production of neurotoxic forms of amyloid beta-peptide and by perturbing cellular calcium homeostasis. Damage to oligodendrocytes induced by a demyelinating agent is enhanced, and spatial learning is impaired in PS1 mutant knockin mice. Oligodendrocytes from PS1 mutant knockin mice are more vulnerable to being killed by glutamate and amyloid beta-peptide, and exhibit an abnormality in calcium regulation which is responsible for their death. These findings demonstrate an adverse effect of a disease-causing PS1 mutation in oligodendrocytes, and suggest a mechanism responsible for white matter damage in AD and a contribution of such damage to cognitive impairment. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 48 TC 35 Z9 36 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 3 IS 1 BP 53 EP 64 DI 10.1385/NMM:3:1:53 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 655BL UT WOS:000181531400005 PM 12665676 ER PT J AU Mattson, MP AF Mattson, MP TI Excitotoxic and excitoprotective mechanisms - Abundant targets for the prevention and treatment of neurodegenerative disorders SO NEUROMOLECULAR MEDICINE LA English DT Review DE Alzheimer's disease; apoptosis; calcium; glutamate; Huntington's disease; mitochondria; neurotrophic factor; oxidative stress; Parkinson's disease; stroke ID AMYLOID BETA-PEPTIDE; FIBROBLAST-GROWTH-FACTOR; METHYL-D-ASPARTATE; AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN-INJURY; SPINAL-CORD-INJURY; FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE-SYNTHASE; PROTECT HIPPOCAMPAL-NEURONS; LIPID-PEROXIDATION PRODUCT AB Activation of glutamate receptors can trigger the death of neurons and some types of glial cells, particularly when the cells are coincidentally subjected to adverse conditions such as reduced levels of oxygen or glucose, increased levels of oxidative stress, exposure to toxins or other pathogenic agents, or a disease-causing genetic mutation. Such excitotoxic cell death involves excessive calcium influx and release from internal organelles, oxyradical production, and engagement of programmed cell death (apoptosis) cascades. Apoptotic proteins such as p53, Bax, and Par-4 induce mitochondrial membrane permeability changes resulting in the release of cytochrome c and the activation of proteases, such as caspase-3. Events occurring at several subcellular sites, including the plasma membrane, endoplasmic reticulum, mitochondria and nucleus play important roles in excitotoxicity. Excitotoxic cascades are initiated in postsynaptic dendrites and may either cause local degeneration or plasticity of those synapses, or may propagate the signals to the cell body resulting in cell death. Cells possess an array of anti-excitotoxic mechanisms including neurotrophic signaling pathways, intrinsic stress-response pathways, and survival proteins such as protein chaperones, calcium-binding proteins, and inhibitor of apoptosis proteins. Considerable evidence supports roles for excitotoxicity in acute disorders such as epileptic seizures, stroke and traumatic brain and spinal cord injury, as well as in chronic age-related disorders such as Alzheimer's, Parkinson's, and Huntington's disease and amyotrophic lateral sclerosis. A better understanding of the excitotoxic process is not only leading to the development of novel therapeutic approaches for neurodegenerative disorders, but also to unexpected insight into mechanisms of synaptic plasticity. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 281 TC 296 Z9 317 U1 3 U2 17 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 3 IS 2 BP 65 EP 94 DI 10.1385/NMM:3:2:65 PG 30 WC Neurosciences SC Neurosciences & Neurology GA 683QR UT WOS:000183161300001 PM 12728191 ER PT J AU Pak, KJ Chan, SL Mattson, MP AF Pak, KJ Chan, SL Mattson, MP TI Homocysteine and folate deficiency sensitize oligodendrocytes to the cell death-promoting effects of a presenilin-1 mutation and amyloid beta-peptide SO NEUROMOLECULAR MEDICINE LA English DT Article DE Alzheimer's disease; apoptosis; folic acid; p53 tumor suppressor; PARP; stroke; white matter ID ALZHEIMERS-DISEASE; DNA-DAMAGE; HIPPOCAMPAL-NEURONS; INCREASED VULNERABILITY; PARKINSONS-DISEASE; PRECURSOR PROTEIN; OXIDATIVE STRESS; WHITE-MATTER; RISK-FACTORS; APOPTOSIS AB Although damage to white matter occurs in the brains of patients with Alzheimer's disease (AD), the underlying mechanisms are unknown. Recent findings suggest that individuals with elevated levels of homocysteine are at increased risk of AD. Here we show that oligodendrocytes from mice expressing a mutant form of presenilin-1 (PS1) that causes familial AD exhibit increased sensitivity to death induced by homocysteine compared to oligodendrocytes from wild-type control mice. Homocysteine also sensitized oligodendrocytes to the cytotoxicity of amyloid beta-peptide. Folate deficiency, which is known to result in elevated levels of homocysteine in vivo, also sensitized oligodendrocytes to the cell-death-promoting actions of mutant PS1 and amyloid beta-peptide. Inhibitors of poly (ADP-ribose) polymerase and p53 protected oligodendrocytes against cell death induced by homocysteine and amyloid beta-peptide, consistent with a role for a DNA-damage response in the cell death process. These findings demonstrate an adverse effect of homocysteine on oligodendrocytes, and suggest roles for homocysteine and folate deficiency in the white matter damage in AD and related neurodegenerative disorders. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 47 TC 18 Z9 18 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 3 IS 2 BP 119 EP 127 DI 10.1385/NMM:3:2:119 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 683QR UT WOS:000183161300004 PM 12728194 ER PT J AU Gilman, CP Chan, SL Guo, ZH Zhu, XX Greig, N Mattson, MP AF Gilman, CP Chan, SL Guo, ZH Zhu, XX Greig, N Mattson, MP TI p53 is present in synapses where it mediates mitochondrial dysfunction and synaptic degeneration in response to DNA damage, and oxidative and excitotoxic insults SO NEUROMOLECULAR MEDICINE LA English DT Article DE apoptosis; cerebral cortex; synaptosomes; transcription ID AMYLOID BETA-PEPTIDE; BREAK-INDUCED APOPTOSIS; NEURONAL DEATH; CELL-DEATH; PROTECTS NEURONS; IN-VIVO; STRESS; BAX; ACTIVATION; INHIBITOR AB A form of programmed cell-death called apoptosis occurs in neurons during development of the nervous system, and may also occur in a variety of neuropathological conditions. Here we present evidence obtained in studies of adult mice and neuronal cell cultures showing that p53 protein is present in synapses where its level and amount of phosphorylation are increased following exposure of the cells to the DNA-damaging agent etoposide. We also show that levels of active p53 increase in isolated cortical synaptosomes exposed to oxidative and excitotoxic insults. Increased levels of p53 also precede loss of synapsin I immunoreactive terminals in cultured hippocampal neurons exposed to etoposide. Synaptosomes from p53-deficient mice exhibit increased resistance to oxidative and excitotoxic insults as indicated by stabilization of mitochondrial membrane potential and decreased production of reactive oxygen species. Finally, we show that a synthetic inhibitor of p53 (PFT-alpha) protects synaptosomes from wild-type mice against oxidative and excitotoxic injuries, and preserves presynaptic terminals in cultured hippocampal neurons exposed to etoposide. Collectively, these findings provide the first evidence for a local transcription-independent action of p53 in synapses, and suggest that such a local action of p53 may contribute to the dysfunction and degeneration of synapses that occurs in various neurodegenerative disorders. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 65 TC 55 Z9 59 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 3 IS 3 BP 159 EP 172 DI 10.1385/NMM:3:3:159 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 702ZB UT WOS:000184254000003 PM 12835511 ER PT J AU Haughey, NJ Mattson, MP AF Haughey, NJ Mattson, MP TI Alzheimer's amyloid beta-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes SO NEUROMOLECULAR MEDICINE LA English DT Article DE ATP; cerebral cortex; connexin; glutamate; octanol; suramin ID IMPAIRS GLUTAMATE TRANSPORT; MEMBRANE LIPID-PEROXIDATION; RAT CORTICAL ASTROCYTES; CULTURED ASTROCYTES; NITRIC-OXIDE; CA2+ HOMEOSTASIS; GAP-JUNCTIONS; CELL-DEATH; DISEASE; RELEASE AB Alzheimer's disease (AD) involves the progressive extracellular deposition of amyloid P-peptide (Abeta), a self-aggregating 40-42 amino acid protein that can damage neurons resulting in their dysfunction and death. Studies of neurons have shown that Abeta perturbs cellular-calcium homeostasis so that calcium responses to agonists that induce calcium influx or release from internal stores are increased. The recent discovery of intercellular calcium waves in astrocytes suggests intriguing roles for astrocytes in the long-range transfer of information in the nervous system. We now report that Abeta alters calcium-wave signaling in cultured rat cortical astrocytes. Exposure of astrocytes to AbetaI-42 resulted in an increase in the amplitude and velocity of evoked calcium waves, and increased the distance the waves traveled. Suramin decreased wave propagation in untreated astrocytes and abrogated the enhancing effect of Abeta on calcium-wave amplitude and velocity, indicating a requirement for extracellular ATP in wave propagation. Treatment of astrocytes with an uncoupler of gap junctions did not significantly reduce the amplitude, velocity, or distance of calcium waves in control cultures, but completely abolished the effects of Abeta on each of the three wave parameters. These findings reveal a novel action of Abeta on the propagation of intercellular calcium signals in astrocytes, and also suggests a role for altered astrocyte calcium-signaling in the pathogenesis of AD. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 46 TC 49 Z9 51 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2003 VL 3 IS 3 BP 173 EP 180 DI 10.1385/NMM:3:3:173 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 702ZB UT WOS:000184254000004 PM 12835512 ER PT S AU Herning, RI Better, W Tate, K Cadet, JL AF Herning, RI Better, W Tate, K Cadet, JL BE Slikker, W Andrews, RJ Trembly, B TI EEG deficits in chronic marijuana abusers during monitored abstinence - Preliminary findings SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE EEG deficits; marijuana abuse ID CANNABIS USE; ALCOHOLICS AB Cognitive, cerebrovascular, and psychiatric impairments have been documented with chronic marijuana users. To better understand the nature and duration of these neurocognitive changes in marijuana abusers, we recorded the resting EEG of 29 abstinent chronic marijuana abusers and 21 control subjects. The marijuana abusers were tested twice: the first evaluation occurred within 72 hours of admission to the inpatient research unit; the second evaluation occurred after 28 to 30 days of monitored abstinence. A three-minute period of EEG was recorded during resting eyes-closed conditions from eight electrodes (F-3, C-3, P-3, O-1, F-4 C-4, P-4, and O-2). The artifacted EEG was converted to six frequency bands (delta, theta, alpha(1), alpha(2) ,beta(1), and beta(2)) using a fast Fourier transform. During early abstinence, absolute power was significantly lower (p < 0.05) for the marijuana abusers than for the control subjects for the theta and alpha(1) bands. These reductions in theta and alpha(1) power persisted for 28 days of monitored abstinence. These EEG changes, together with cerebral blood flow deficits, might underlie the cognitive alterations observed in marijuana abusers. Additional research is needed to determine how long these deficits persist during abstinence and if treatment with neuroprotective agents may reverse them. C1 NIDA, Mol Neuropsychiat Sect, NIH, IRP, Baltimore, MD 21224 USA. RP Herning, RI (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, IRP, POB 5180, Baltimore, MD 21224 USA. NR 17 TC 6 Z9 6 U1 2 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 75 EP 78 PG 4 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000008 PM 12853297 ER PT S AU Jiang, XY Zhu, DM Okagaki, P Lipsky, R Wu, X Banaudha, K Mearow, K Strauss, KI Marini, AM AF Jiang, XY Zhu, DM Okagaki, P Lipsky, R Wu, X Banaudha, K Mearow, K Strauss, KI Marini, AM BE Slikker, W Andrews, RJ Trembly, B TI N-methyl-D-aspartate and TrkB receptor activation in cerebellar granule cells - An in vitro model of preconditioning to stimulate intrinsic survival pathways in neurons SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE N-methyl-D-aspartate; TrkB; receptor activation; cerebellar granular cells; survival pathways; neurons ID NERVE GROWTH-FACTOR; CORTICAL SPREADING DEPRESSION; NEUROTROPHIC FACTOR; KAPPA-B; ISCHEMIC TOLERANCE; PROTEIN-KINASE; MEDIATED NEUROPROTECTION; PROTOONCOGENE PRODUCT; HIPPOCAMPAL-NEURONS; SIGNALING PATHWAYS AB Delineating the mechanisms of survival pathways that exist in neurons will provide important insight into how neurons utilize intracellular proteins as neuroprotectants against the causes of acute neurodegeneration. We have employed cultured rat cerebellar granule cells as a model for determining the mechanisms of these intraneuronal survival pathways. Glutamate has long been known to kill neurons by an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Paradoxically, subtoxic concentrations of NMDA protect neurons against glutamate-mediated excitotoxicity. Because NMDA protects neurons in physiologic concentrations of glucose and oxygen, we refer to this phenomenon as physiologic preconditioning. One of the major mechanisms of NMDA neuroprotection involves the activation of NMDA receptors leading to the rapid release of brain-derived neurotrophic factor (BDNF). BDNF then binds to and activates its cognate receptor, receptor tyrosine kinase B (TrkB). The efficient utilization of these two, receptors confers remarkable resistance against millimolar concentrations of glutamate that kill more than eighty percent of the neurons in the absence of preconditioning the neurons with a subtoxic concentration of NMDA. Exactly how the neurons mediate neuroprotection by activation of both receptors is just beginning to be understood. Both NMDA and TrkB receptors activate nuclear factor kappaB (NF-kappaB), a transcription factor known to be involved in protecting neurons against many different kinds of toxic insults. By converging on survival transcription factors, such as NF-kappaB, NMDA and TrkB receptors protect neurons. Thus, crosstalk between these very different receptors provides a rapid means of neuronal communication to upregulate survival proteins through release and transcriptional activation of messenger RNA. C1 Uniformed Serv Univ Hlth Sci, Dept Neurol & Neurosci, Bethesda, MD 20814 USA. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Mem Univ Newfoundland, Fac Med, St Johns, NF, Canada. RP Marini, AM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol, Bldg A,Room 1036,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. OI Lipsky, Robert/0000-0001-7753-1473 FU NINDS NIH HHS [R01 NS038654] NR 47 TC 51 Z9 54 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 134 EP 145 PG 12 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000017 PM 12853306 ER PT J AU Winkler, D Pjrek, E Pezawas, L Presslich, O Tauscher, J Kasper, S AF Winkler, D Pjrek, E Pezawas, L Presslich, O Tauscher, J Kasper, S TI Relationship between power spectra of the awake EEG and psychomotor activity patterns measured by short-term actigraphy SO NEUROPSYCHOBIOLOGY LA English DT Article DE activity monitoring; arousal; electroencephalography; psychomotor activity; spectral analysis; vigilance ID ANALYSIS SOFTWARE ADAS; QUANTITATIVE EEG; BENZODIAZEPINE DEPENDENCE; WRIST ACTIVITY; SLEEP; DISORDERS; SCHIZOPHRENIA; CARBAMAZEPINE; DEPRESSIVES; PERFORMANCE AB Actigraphy is a quantitative method for the measurement of motor activity. In the present study, actigraphy was used to examine psychomotor correlates of brain activity. Thirty-four psychiatric patients (17 males and 17 females) with different diagnoses participated in this investigation. Directly after EEG recording, motor activity was measured with a wrist actimeter for 15 min in patients in the sitting position. The EEG was quantified by spectrum analysis, and the power spectra as well as other EEG-derived variables were correlated with actigraphic parameters. Occipital and temporoparietal 1 power was statistically significantly higher in patients with higher activity scores and lower in those with a high density of sleep (SB) or wake bouts (WB). A high density of SB or WB was also positively correlated with higher mean alpha power. Immobile phases measured by actigraphy were positively associated with occipital alpha and with frontal/frontopolar delta activity, preferentially on the side of the left hemisphere. Our results, while preliminary, suggest that short-term actigraphy may be apt to reflect central nervous system arousal. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Hosp Psychiat, Dept Gen Psychiat, AT-1090 Vienna, Austria. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Winkler, D (reprint author), Univ Hosp Psychiat, Dept Gen Psychiat, Wahringer Gurtel 18-20, AT-1090 Vienna, Austria. RI Pezawas, Lukas/A-2367-2011; Tauscher, Johannes/M-5976-2016 OI Pezawas, Lukas/0000-0002-1329-6352; NR 44 TC 3 Z9 3 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2003 VL 48 IS 4 BP 176 EP 181 DI 10.1159/000074634 PG 6 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 753BE UT WOS:000187210900002 PM 14673214 ER PT J AU Doyon, J Penhune, V Ungerleider, LG AF Doyon, J Penhune, V Ungerleider, LG TI Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning SO NEUROPSYCHOLOGIA LA English DT Article DE cortico-striatal systems; cortico-cerebellar systems; motor skill learning; motor required learning; motor adaptation; PET; EURI ID POSITRON EMISSION TOMOGRAPHY; BASAL GANGLIA; VISUOMOTOR SEQUENCE; HUNTINGTONS-DISEASE; FUNCTIONAL-ANATOMY; PARKINSONS-DISEASE; MEMORY-SYSTEMS; FRONTAL LOBES; TIME-COURSE; CORTEX AB This review paper focuses on studies in healthy human subjects that examined the functional neuroanatomy and cerebral plasticity associated with the learning, consolidation and retention phases of motor skilled behaviors using modern brain imaging techniques. Evidence in support of a recent model proposed by Doyon and Ungerleider [Functional Anatomy of Motor Skill Learning. In: Squire LR, Schacter DL, editors. Neuropsychology of Memory. New York: Guilford Press, 2002.] is also discussed. The latter suggests that experience-dependent changes in the brain depend not only on the stage of learning, but also on whether subjects are required to learn a new sequence of movements (motor sequence learning) or learn to adapt to environmental perturbations (motor adaptation). This model proposes that the cortico-striatal and cortico-cerebellar systems contribute differentially to motor sequence learning and motor adaptation, respectively, and that this is most apparent during the slow learning phase (i.e. automatization) when subjects achieve asymptotic performance, as well as during reactivation of the new skilled behavior in the retention phase. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. Concordia Univ, Dept Psychol, Montreal, PQ H4B 1R6, Canada. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Doyon, J (reprint author), Univ Montreal, Dept Psychol, CP 6128,Downtown Stn, Montreal, PQ H3C 3J7, Canada. NR 69 TC 416 Z9 418 U1 1 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2003 VL 41 IS 3 BP 252 EP 262 AR PII S0028-3932(02)00158-6 DI 10.1016/S0028-3932(02)00158-6 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 626TQ UT WOS:000179889700003 PM 12457751 ER PT J AU Richell, RA Mitchell, DGV Newman, C Leonard, A Baron-Cohen, S Blair, RJR AF Richell, RA Mitchell, DGV Newman, C Leonard, A Baron-Cohen, S Blair, RJR TI Theory of mind and psychopathy: can psychopathic individuals read the 'language of the eyes'? SO NEUROPSYCHOLOGIA LA English DT Article DE psychopathy; theory of mind; amygdala ID ASPERGER-SYNDROME; AUTISM; ADULTS AB There have been suggestions that Theory of Mind (ToM) impairment might lead to aggressive behaviour and psychopathy. Psychopathic and matched non-psychopathic individuals, as defined by the Hare Psychopathy Checklist [The Hare Psychopath Checklist-Revised, 1991] completed the 'Reading the Mind in the Eyes' ToM Test [Journal of Child Psychology and Psychiatry, 1997;38:813]. This test requires the self-paced identification of mental states from photographs of the eye region alone. Results indicated that the psychopathic individuals did not present with any generalised impairment in ToM. The data are discussed with reference to the putative neural system mediating performance on this task and models of psychopathy. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. UCL, Dept Psychol, Inst Cognit Sci, London, England. HMP Wormwood Scrubs, London, England. Univ Cambridge, Dept Expt Psychol, Autism Res Ctr, Cambridge CB2 3EB, England. Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 3EB, England. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, 15K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 16 TC 165 Z9 170 U1 8 U2 46 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2003 VL 41 IS 5 BP 523 EP 526 AR PII S0028-3932(02)00175-6 DI 10.1016/S0028-3932(02)00175-6 PG 4 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 654FQ UT WOS:000181483900001 PM 12559146 ER PT J AU Sanfey, AG Hastie, R Colvin, MK Grafman, J AF Sanfey, AG Hastie, R Colvin, MK Grafman, J TI Phineas gauged: decision-making and the human prefrontal cortex SO NEUROPSYCHOLOGIA LA English DT Article DE decision-making; risk; frontal lobes ID POSTERIOR BRAIN-DAMAGE; PROSPECT-THEORY; RISK; CHOICE AB Poor social judgment and decision-making abilities have often been attributed to people who have suffered injury to the ventromedial prefrontal cortex (VMPFC). However, few laboratory tests of decision-making have been conducted on these patients. The exception to this is the Iowa Gambling Task which has often, but not always, demonstrated differential performance between patients and controls. Results from patients with prefrontal cortex lesions on a novel test of decision-making are presented. Participants explored and chose from pairs of gambles that differed in their underlying distributions, primarily in the variance of their respective outcomes. In accordance with many findings from the behavioral decision-making literature, both young normal participants and older patient controls demonstrated a marked avoidance of risk and selected largely from secure, low variance gambles. In contrast, patients with ventromedial lesions were divided into two clear sub-groups. One group behaved similarly to normals, showing a risk-averse strategy. The other group displayed a distinctive risk-seeking behavior pattern, choosing predominantly from the high-variance, high-risk decks. This research demonstrates some of the advantages of using methods and theories from traditional decision-making research to study the behavior of patients, as well as the benefits of examining individual participants, and provides new insights into the nature of the decision-making deficit in patients with ventromedial prefrontal cortex lesions. Published by Elsevier Science Ltd. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. Princeton Univ, Princeton, NJ 08544 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. RI Sanfey, Alan/D-2350-2010; Henrich, Joseph/A-2403-2009; OI Grafman, Jordan H./0000-0001-8645-4457 NR 22 TC 64 Z9 65 U1 17 U2 39 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2003 VL 41 IS 9 BP 1218 EP 1229 DI 10.1016/S0028-3932(03)00039-3 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 688ME UT WOS:000183438400008 PM 12753961 ER PT J AU Horwitz, B Amunts, K Bhattacharyya, R Patkin, D Jeffries, K Zilles, K Braun, AR AF Horwitz, B Amunts, K Bhattacharyya, R Patkin, D Jeffries, K Zilles, K Braun, AR TI Activation of Broca's area during the production of spoken and signed language: a combined cytoarchitectonic mapping and PET analysis SO NEUROPSYCHOLOGIA LA English DT Article DE neuroimaging; American Sign Language; brain; human; Brodmann areas ID POSITRON EMISSION TOMOGRAPHY; INFERIOR PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; SENTENCE COMPREHENSION; NEURAL ORGANIZATION; SPEECH; BRAIN; DEAF; RECOGNITION; SEMANTICS AB Broca's area in the inferior frontal gyrus consists of two cytoarchitectonically defined regions-Brodmann areas (BA) 44 and 45. Combining probabilistic maps of these two areas with functional neuroimaging data obtained using PET, it is shown that BA45, not BA44, is activated by both speech and signing during the production of language narratives in bilingual subjects fluent from early childhood in both American Sign Language (ASL) and English when the generation of complex movements and sounds is taken into account. It is BA44, not BA45, that is activated by the generation of complex articulatory movements of oral/laryngeal or limb musculature. The same patterns of activation are found for oral language production in a group of English speaking monolingual subjects. These findings implicate BA45 as the part of Broca's area that is fundamental to the modality-independent aspects of language generation. Published by Elsevier Ltd. C1 Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA. Res Ctr, Inst Med, D-52428 Julich, Germany. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bldg 10,Rm 6C420,MSC 1591, Bethesda, MD 20892 USA. RI Amunts, Katrin/I-3470-2013; Zilles, Karl/J-9704-2013; OI Amunts, Katrin/0000-0001-5828-0867; Zilles, Karl/0000-0001-9296-9959; Zilles, Karl/0000-0002-4705-4175 NR 52 TC 76 Z9 81 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2003 VL 41 IS 14 BP 1868 EP 1876 DI 10.1016/S0028-3932(03)00125-8 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 745GH UT WOS:000186680600002 PM 14572520 ER PT J AU Rogers, RD Tunbridge, EM Bhagwagar, Z Drevets, WC Sahakian, BJ Carter, CS AF Rogers, RD Tunbridge, EM Bhagwagar, Z Drevets, WC Sahakian, BJ Carter, CS TI Tryptophan depletion alters the decision-making of healthy volunteers through altered processing of reward cues SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE tryptophan depletion; serotonin; decision-making; orbitotrontal cortex; risk-aversion and risk-seeking ID PREFRONTAL CORTEX; DISCRIMINATIVE STIMULUS; SEROTONIN NEURONS; PROSPECT-THEORY; COCAINE; 5-HYDROXYTRYPTAMINE; MECHANISMS; DEPRESSION; DOPAMINE; RATS AB While accumulating evidence suggests that effective real-life decision-making depends upon the functioning of the orbitofrontal cortex, much less is known about the involvement of the monoamine neurotransmitter systems and, in particular, serotonin. In the present study, we explored the impact of depleting the serotonin precursor, tryptophan, on human decision-making. Eighteen healthy volunteers consumed an amino-acid drink containing tryptophan and 18 healthy volunteers consumed an amino-acid drink without tryptophan, before choosing between simultaneously presented gambles, differing in the magnitude of expected gains (ie reward), the magnitude of expected losses (ie punishment), and the probabilities with which these outcomes were delivered. Volunteers also chose between gambles probing identified non-nomative biases in human decision-making, namely, risk-aversion when choosing between gains and risk-seeking when choosing between losses. Tryptophan-depleted volunteers showed reduced discrimination between magnitudes of expected gains associated with different choices. There was little evidence that tryptophan depletion was associated with altered discrimination between the magnitudes of expected losses, or altered discrimination between the relative probabilities with which these positive or negative outcomes were delivered. Risk-averse and risk-seeking biases were also unchanged. These results suggest that serotonin mediates decision-making in healthy volunteers by modulating the processing of reward cues, perhaps represented within the orbitofrontal cortex. It is possible that such a change in the cognition mediating human choice is one mechanism associated with the onset and maintenance of anhedonia and lowered mood in psychiatric illness. C1 Univ Oxford, Dept Psychiat, Oxford, England. NIMH, Sect Mood & Anxiety Disorders Neuroimaging, NIH, Washington, DC USA. Univ Cambridge, Dept Psychiat, Cambridge, England. Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA USA. RP Rogers, RD (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. RI Bhagwagar, Zubin/H-1071-2012; OI Bhagwagar, Zubin/0000-0002-1101-768X; Tunbridge, Elizabeth/0000-0002-2966-2281 NR 54 TC 188 Z9 194 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2003 VL 28 IS 1 BP 153 EP 162 DI 10.1038/sj.npp.1300001 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 642GT UT WOS:000180796400018 PM 12496952 ER PT J AU Funk, D Li, Z Shaham, Y Le, AD AF Funk, D Li, Z Shaham, Y Le, AD TI Effect of blockade of corticotropin-releasing factor receptors in the median raphe nucleus on stress-induced c-fos mRNA in the rat brain SO NEUROSCIENCE LA English DT Article DE central nucleus of the amygdala; 5-hydroxytryptamine; in situ hybridization; reinstatement; relapse ID COCAINE-SEEKING; ALCOHOL-SEEKING; INDUCED REINSTATEMENT; PRIMING INJECTIONS; STRIA TERMINALIS; INDUCED RELAPSE; BED NUCLEUS; NEUROBIOLOGY; MECHANISMS; BEHAVIOR AB Using a rat relapse model, we have shown that infusion of a corticotropin-releasing factor (CRF) receptor antagonist into the median raphe nucleus (MRN) blocks foot-shock stress-induced reinstatement of alcohol seeking in rats. The goal of the present study was to begin identifying brain sites potentially involved in this effect. For this purpose, we measured levels of c-fos mRNA in discrete nuclei of the rat brain following exposure to intermittent footshock, which was preceded by intra-MRN infusions of a CRF receptor antagonist, d-Phe CRF (0 or 50 ng). Exposure to intermittent footshock increased the expression of c-fos mRNA in a number of brain regions previously shown to be responsive to stressful stimuli. Pretreatment with d-Phe CRF in the MRN selectively attenuated the increases in c-fos mRNA induced by footshock in the central nucleus of the amygdala (CeA). These findings are consistent with previous data on the important role for the CeA in stress-induced reinstatement of drug seeking. These results also suggest that inhibition of CeA activity may contribute to the blockade of alcohol-seeking induced by footshock that we have observed following injections of d-Phe into the MRN. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Ctr Addict & Mental Hlth, Dept Neurosci, Toronto, ON M5S 2S1, Canada. Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A8, Canada. NIDA, Behav Neurosci Branch, Intramural Res Program, DHHSNIH, Baltimore, MD 21044 USA. RP Funk, D (reprint author), Ctr Addict & Mental Hlth, Dept Neurosci, Toronto, ON M5S 2S1, Canada. RI shaham, yavin/G-1306-2014 FU NIAAA NIH HHS [AA13108] NR 24 TC 25 Z9 26 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 122 IS 1 BP 1 EP 4 DI 10.1016/S0306-4522(03)00623-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 743QE UT WOS:000186584400001 PM 14596843 ER PT J AU Dobolyi, A Palkovits, M Bodnar, I Usdin, TB AF Dobolyi, A Palkovits, M Bodnar, I Usdin, TB TI Neurons containing tuberoinfundibular peptide of residues project to limbic, endocrine, auditory and spinal areas in rat SO NEUROSCIENCE LA English DT Article DE TIP39 immunocytochemistry; electrolytic lesion; subparafascicular nucleus; medial paralemniscal nucleus ID PITUITARY-ADRENOCORTICAL AXIS; PLASMA-CORTICOSTERONE RESPONSES; BRAIN-STEM; STRIA TERMINALIS; BED NUCLEUS; PARAVENTRICULAR NUCLEUS; ELECTRICAL-STIMULATION; EFFERENT PROJECTIONS; AMYGDALOID COMPLEX; VENTRAL SUBICULUM AB Accumulating evidence suggests that tuberoinfundibular peptide of 39 residues (TIP39) may be the endogenous ligand of the parathyroid hormone 2 receptor. The vast majority of TIP39-containing neurons are localized in two regions, the subparafascicular area at the thalamic-mid brain junction, and the medial paralemniscal nucleus in the rostral pons. In contrast to the restricted localization of TIP39-containing cell bodies, TIP39-containing fibers have a widespread distribution. TIP39 neurons were lesioned electrolytically to determine the origin of TIP39-containing fibers within different parts of the rat CNS. Following bilateral lesions of the medial subparafascicular area including the subparafascicular nucleus, TIP39-immunoreactive fibers almost completely disappeared from forebrain regions including the anterior limbic cortical areas, the shell and cone portions of the nucleus accumbens, the lateral septum, the bed nucleus of the stria terminalis, the amygdaloid nuclei, the fundus striati, the subiculum, the thalamic paraventricular nucleus, and the hypothalamic paraventricular, dorsomedial and arcuate nuclei. Unilateral lesions of the medial and the lateral subparafascicular area demonstrated that the projections are ipsilateral and that medial lesions produce higher reductions in the density of TIP39 fibers except in the amygdala and the hypothalamus. Following lesions of the medial paralemniscal nucleus, TIP39-immunoreactive fibers disappeared from the medial geniculate, body, the periaqueductal gray, the deep layers of the superior colliculus, the external cortex of the inferior colliculus, the cuneiform nucleus, the nuclei of the lateral lemniscus, the lateral parabrachial nucleus, the locus coeruleus, the subcoeruleus area, the medial nucleus of the trapezoid body, the periolivary nuclei, and the spinal cord, suggesting that these regions receive TIP39-containing fibers from the medial paralemniscal nucleus, and unilateral lesions demonstrated that the projections are ipsilateral. The projections of the TIP39-containing cells in the subparafascicular area suggest their involvement in limbic and endocrine functions, while the projections of the TIP39-containing cells in the medial paralemniscal nucleus suggest their involvement in auditory and nociceptive functions. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Anat, Neuromorphol Lab, H-1094 Budapest, Hungary. Semmelweis Univ, Dept Human Morphol & Dev Biol, Neuroendocrine Res Lab, H-1094 Budapest, Hungary. RP Usdin, TB (reprint author), NIMH, Genet Lab, 36 Convent Dr,MSC 4094,Bldg 36,Room 3D06, Bethesda, MD 20892 USA. EM usdin@codon.nih.gov RI Dobolyi, Arpad/B-9089-2008; Palkovits, Miklos/F-2707-2013 NR 45 TC 36 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 122 IS 4 BP 1093 EP 1105 DI 10.1016/j.neuroscience.2003.08.034 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 751PD UT WOS:000187075400020 PM 14643775 ER PT J AU Yao, PJ Zhang, P Mattson, MP Furukawa, K AF Yao, PJ Zhang, P Mattson, MP Furukawa, K TI Heterogeneity of endocytic proteins: Distribution of clathrin adaptor proteins in neurons and glia SO NEUROSCIENCE LA English DT Article DE AP180; AP2; CALM; epsin 1; clathrin adaptor; synapse ID SYNAPTIC VESICLE ENDOCYTOSIS; ASSEMBLY PROTEIN; COATED PITS; MEDIATED ENDOCYTOSIS; ALZHEIMERS-DISEASE; PLASMA-MEMBRANE; SORTING SIGNALS; ENTH DOMAIN; AP180; BINDING AB Clathrin adaptor protein (AP)180 is a synaptic protein that regulates the assembly of clathrin-coated vesicles. Several endocytic proteins including AP2, CALM, and epsin 1 have functions or molecular structures similar to AP180. We determined if AP180 associates with functional synapses in cultured hippocampal neurons. We also compared the expression pattern of AP180 with the other endocytic proteins. The distribution of AP180 corresponded with the synaptic vesicle-associated protein synapsin 1, and with functional presynaptic terminals labeled with the styryl dye FM1-43. Synaptic AP2 colocalized with AP180, but the distribution of AP2 was not limited to synapses of neurons and it was also expressed in glia. CLAM and epsin 1 immunoreactivities were also detected in both neurons and glia. Unlike AP180, the neuronal immunoreactivity of CALM was not intense in the synaptic puncta. Epsin 1 immunoreactivity was found in both synaptic and extrasynaptic sites, and its synaptic distribution only partially overlapped with that of AP180. These results support roles for AP180 in synaptic function in neurons. The findings also provide information on the distribution of AP2, CALM, and epsin 1 in cells of the nervous system that suggest different roles for these endocytic proteins in the biology of these cells. Published by Elsevier Ltd on behalf of IBRO. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Yao, PJ (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 57 TC 18 Z9 19 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 121 IS 1 BP 25 EP 37 DI 10.1016/S0306-4522(03)00431-7 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 720ML UT WOS:000185264500004 PM 12946697 ER PT J AU Umegaki, H Ishiwata, K Ogawa, O Ingram, DK Roth, GS Oda, K Kurotani, S Kawamura, K Wang, WF Ikari, H Senda, M AF Umegaki, H Ishiwata, K Ogawa, O Ingram, DK Roth, GS Oda, K Kurotani, S Kawamura, K Wang, WF Ikari, H Senda, M TI Longitudinal follow-up study of adenoviral vector-mediated gene transfer of dopamine D-2 receptors in the striatum in young, middle-aged, and aged rats: A positron emission tomography study SO NEUROSCIENCE LA English DT Article DE aging; autoradiography; raclopride; binding potential ID D-2 RECEPTOR; C-11 NEMONAPRIDE; BRAIN; EXPRESSION; THERAPY; VIVO; PET; INFLAMMATION; RACLOPRIDE; ACTIVATION AB Overexpression of dopamine D-2 receptors by adenoviral vector-mediated gene transfer in the rat striatum was evaluated by positron emission tomography in vivo and by ex vivo autoradiography in 5-, 13-, and 24-month-old Fischer 344 rats. Each rat had hemilateral gene transfer of D-2 receptors mediated by adenoviral vectors (AdCMV.DopD(2)R) in the striatum with contralateral striatal injection of control vectors (AdCMV.LacZ). At day 2 or 3 after vector injection positron emission tomography or ex vivo autoradiography was performed. The binding potential of a radiolabeled D-2 receptors ligand, [C-11]raclopride, was significantly higher in the D-2 receptors gene-transferred striatum than the control side in each age group at a similar degree. The binding potential in the AdCMV.DopD(2)R-injected striatum of 24-month-old rats was similar to that in the AdCMV.LacZ-injected striatum of 5-month-old rats (0.99+/-0.14 versus 0.91+/-0.08). A significant age-associated decrease of the binding potential of [C-11]raclopride was found in the control vector-injected side, and a significant increase of the binding potential in the adenoviral vector-injected side in all three age groups, suggesting no aging effect on the overexpression of D-2 receptors. A group of rats underwent follow-up assessment by positron emission tomography. The overexpression of D-2 receptors decreased with time in all three groups; however, the decrease rate of the D-2 receptors expression was significantly smaller in the 24-month-old group than in the 5-month-old group. We confirmed that the adenoviral vector-mediated gene transfer of D-2 receptors compensated the decreased density of striatal D-2 receptors in the 24-month-old rats up to the level in the control striatum of 5-month-old rats, and the decrease rate of the overexpression was significantly smaller in aged rats. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Nagoya Univ, Grad Sch Med, Dept Geriatr, Showa Ku, Nagoya, Aichi 466, Japan. Tokyo Metropolitan Inst Gerontol, Positron Med Ctr, Itabashi Ku, Tokyo 1730022, Japan. NIA, Gerontol Res Ctr, Lab Expt Geront, NIH, Baltimore, MD 21224 USA. Fukushimura Hosp, Choju Med Inst, Toyohashi, Aichi 4418124, Japan. RP Umegaki, H (reprint author), Nagoya Univ, Grad Sch Med, Dept Geriatr, Showa Ku, 65 Tsuruma Cho, Nagoya, Aichi 466, Japan. NR 35 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 121 IS 2 BP 479 EP 486 DI 10.1016/S0306-4522(03)00489-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 729YW UT WOS:000185803300023 PM 14522006 ER PT J AU Lei, DL Long, JM Hengemihle, J O'Neill, J Manaye, KF Ingram, DK Mouton, PR AF Lei, DL Long, JM Hengemihle, J O'Neill, J Manaye, KF Ingram, DK Mouton, PR TI Effects of estrogen and raloxifene on neuroglia number and morphology in the hippocampus of aged female mice SO NEUROSCIENCE LA English DT Article DE 17 beta estradiol; microglia; astrocytes; stereology; hippocampal formation; raloxifene ID DENDRITIC SPINE DENSITY; PENETRATING BRAIN-INJURY; ALZHEIMERS-DISEASE; REPLACEMENT THERAPY; RAT-BRAIN; SYNAPTIC PLASTICITY; GONADAL-STEROIDS; DENTATE GYRUS; GRANULE CELLS; ESTRADIOL AB Hormone replacement therapy with the gonadal steroid estrogen or synthetic agents such as raloxifene, a selective estrogen receptor modulator, may affect cellular function in brains of postmenopausal women. In vitro studies suggest that 17beta estradiol and raloxifene can alter the microglial and astrocyte expression of immuno-neuronal modulators, such as cytokines, complement factors, chemokines, and other molecules involved in neuroinflammation and neurodegeneration. To directly test whether exogenous 17beta estradiol and raloxifene affect the number of glial cells in brain, C57BL/6NIA female mice aged 20-24 months received bilateral ovariectomy followed by s.c. placement of a 60-day release pellet containing 17beta estradiol (1.7 mg), raloxifene (10 mg), or placebo (cholesterol). After 60 days, numbers of microglia and astrocytes were quantified in dentate gyrus and CA1 regions of the hippocampal formation using immunocytochemistry and design-based stereology. The results show that long-term 17beta estradiol treatment in aged female mice significantly lowered the numbers of astrocytes and microglial cells in dentate gyrus and CA1 regions compared with placebo. After long-term treatment with raloxifene, a similar reduction was observed in numbers of astrocytes and microglial cells in the hippocampal formation. These findings indicate that estrogen and selective estrogen receptor modulators can influence glial-mediated inflammatory pathways and possibly protect against age- and disease-related neuropathology. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Howard Univ, Sch Med, Dept Biophys & Physiol, Washington, DC 20059 USA. Cent S Univ, Xiangya Med Coll, Dept Anat & Neurobiol, Changsha 410078, Hunan, Peoples R China. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. RP Mouton, PR (reprint author), NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moutonpe@grc.nia.nih.gov NR 71 TC 64 Z9 70 U1 4 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 121 IS 3 BP 659 EP 666 DI 10.1016/S0306-4522(03)00245-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 743QC UT WOS:000186584200013 PM 14568026 ER PT J AU Chen, X Levine, JD AF Chen, X Levine, JD TI Altered temporal pattern of mechanically evoked C-fiber activity in a model of diabetic neuropathy in the rat SO NEUROSCIENCE LA English DT Article DE STZ; neuropathic pain; peripheral nociceptor; neural coding ID PAINFUL PERIPHERAL NEUROPATHY; PROTEIN-KINASE-C; SPINAL-CORD; SUBSTANCE-P; IN-VITRO; NERVE; HYPERALGESIA; NOCICEPTORS; CAT; SENSITIZATION AB While enhanced nociceptor activity has been demonstrated in models of painful peripheral neuropathy, analyses of activity pattern, which could play a role in the symptoms experienced as well as help elucidate underlying mechanism, are still limited. We evaluated the pattern of C-fiber activity, in response to mechanical and chemical stimuli, in a rat model of diabetes induced by a pancreatic P-cell toxin, streptozotocin (STZ). In diabetic rats the number of action potentials produced by threshold and suprathreshold (10 g) sustained (60 s) mechanical stimuli was elevated in approximately half of C-fibers. These high-firing C-fibers demonstrated a disproportionate increase in interspike intervals (ISIs) between 100 and 199 ms, compared with low-firing diabetic and control C-fibers. The co-efficient of variability (CV2), a frequency independent measure of ISI variability, was also greater in high-firing fibers, compared with control fibers. Unexpectedly, instantaneous frequency of the initial burst of activity during the first second was lower in high-firing fibers, even though the average frequency over the last 59 s was significantly higher. The number of action potentials evoked by a noxious chemical stimulus, 300 and 600 mM KCl, injected adjacent to the mechanical receptive field was also significantly increased in C-fibers from diabetic rats and mechanically high-firing fibers had more action potentials in response to KCI than control fibers and a disproportionate increase in ISIs between 100 and 199 ms for responses to chemical stimuli appeared only in mechanically high-firing C-fibers, compared with the mechanically low-firing diabetic or control C-fibers. There was, however, no corresponding change in CV2 or instantaneous frequency plots for the response to chemical stimulation in mechanically high-firing fibers, as there was in the response to mechanical stimulation. Our data demonstrate specific changes in firing pattern of high-firing C-fibers in the rat model of painful neuropathy produced by STZ-diabetes that might contribute to the symptoms experienced by patients. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif San Francisco, NIH, Pain Ctr, Div Neurosci,Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, Div Neurosci,Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, Div Neurosci,Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Div Neurosci,Dept Anat, C-522 Box 0440, San Francisco, CA 94143 USA. FU NINDS NIH HHS [NS21647] NR 40 TC 34 Z9 34 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 121 IS 4 BP 1007 EP 1015 DI 10.1016/S0306-4522(03)00486-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA 741QY UT WOS:000186469800021 PM 14580951 ER PT J AU Parada, CA Yeh, JJ Reichling, DB Levine, JD AF Parada, CA Yeh, JJ Reichling, DB Levine, JD TI Transient attenuation of protein kinase C epsilon can terminate a chronic hyperalgesic state in the rat SO NEUROSCIENCE LA English DT Article DE chronic pain; analgesia; epinephrine; adrenergic receptor; repetitive strain ID TRANSLOCATION; SENSITIZATION; ANTAGONIST; PROTECTION; ISOZYME; INJURY; MUSCLE; PAIN; MICE AB Recently we demonstrated that a single 3-day episode of carrageenan-induced acute cutaneous inflammation can create a chronic state of increased susceptibility to inflammatory hyperalgesia. In this latent "primed" state, although there is no ongoing hyperalgesia, the hyperalgesic response to subsequent challenges with inflammatory agent (prostaglandin E-2; PGE(2)) is greatly enhanced. Furthermore, the PGE(2)-induced hyperalgesia in primed skin was found to require activity of the epsilon isozyme of protein kinase C(PKCepsilon), a second messenger that is not required for PGE(2)-induced hyperalgesia in control animals. In the present study we tested the hypothesis that activity of PKCepsilon not only plays a critical role in the expression of primed PGE(2)-induced hyperalgesia, but also in the development and maintenance of the primed state itself. Antisense oligodeoxynucleotide was employed to produce a decrease in PKCepsilon in the nerve, verified by Western blot analysis. PKCepsilon was found to be essential both for the development of carrageenan-induced hyperalgesic priming, as well as for the maintenance of the primed state. Furthermore, hyperalgesic priming could be induced by an agonist of PKCepsilon (pseudo-receptor octapeptide for activated PKCepsilon) at a dose that itself causes no hyperalgesia. The finding that transient inhibition of PKCepsilon can not only prevent the development of priming, but can also terminate a fully developed state of priming suggests the possibility that selective targeting PKCepsilon might be an effective new strategy in the treatment of chronic inflammatory pain. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Calif San Francisco, NIH Pain Ctr, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Program Neurosci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, Dept Oral & Maxillofacial Surg, 521 Parnassus Ave,Room C-555,Campus Box 0440, San Francisco, CA 94143 USA. RI Parada, Carlos Amilcar/C-3974-2012 FU NINDS NIH HHS [NS21647] NR 13 TC 65 Z9 67 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 120 IS 1 BP 219 EP 226 DI 10.1016/S0306-4522(03)00267-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 703AH UT WOS:000184257500020 PM 12849754 ER PT J AU Joseph, EK Levine, JD AF Joseph, EK Levine, JD TI Sexual dimorphism in the contribution of protein kinase C isoforms to nociception in the streptozotocin diabetic rat SO NEUROSCIENCE LA English DT Article DE blood glucose; nociception; sex difference; second messengers; streptozotocin ID ROOT GANGLION NEURONS; NERVE LIGATION PSNL; SENSORY NEUROPATHY; PERIPHERAL NEUROPATHY; PAIN THRESHOLD; GROWTH-FACTOR; FEMALE RATS; DELTA-PKC; GENDER; EPSILON AB The contribution of second messenger signaling, glucose level and sex hormones to sexual dimorphism in the streptozotocin model of diabetic painful peripheral neuropathy was evaluated. Streptozotocin induced elevation of blood glucose and mechanical hyperalgesia (measured by the Randall-Selitto paw-withdrawal test) were both greater in female rats. Ovariectomy abolished and estrogen implants reconstituted this sexual dimorphism; gonadectomy in males had no effect. An inhibitor of protein kinase CE attenuated hyperalgesia in males and ovariectomized females, but not in normal females or in ovariectomized females with estrogen implants, whereas inhibitors of protein kinase Cis an element of attenuated hyperalgesia in females but not in males. Inhibitors of protein kinase A, protein kinase C (non-selective), protein kinase G and nitric oxide synthase attenuated hyperalgesia equally in both sexes. Higher blood glucose levels in diabetic females were also sex hormone dependent, and magnitude of hyperalgesia correlated with blood glucose level in diabetic male and female rats. These results demonstrate sexual dimorphism in diabetic hyperalgesia, mediated by sex hormone dependent differences in protein kinase Cis an element of and protein kinase C-5 signaling and blood glucose levels and suggest that sex may be an important factor to be considered in the treatment of symptomatic diabetic neuropathy. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif San Francisco, Div Neurosci, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neurosci, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. RP Joseph, EK (reprint author), Univ Calif San Francisco, Div Neurosci, Dept Med, Box 0440,Room C522,521 Parnassus Ave, San Francisco, CA 94143 USA. FU NINDS NIH HHS [NS21647] NR 66 TC 40 Z9 44 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 120 IS 4 BP 907 EP 913 DI 10.1016/S0306-4522(03)00400-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 756CH UT WOS:000187447900002 PM 12927197 ER PT J AU Khasar, SG Reichling, DB Green, PG Isenberg, WM Levine, JD AF Khasar, SG Reichling, DB Green, PG Isenberg, WM Levine, JD TI Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat SO NEUROSCIENCE LA English DT Article DE chronic pain; hyperalgesia; parasympathetic nervous system; estrogen; sex; gender ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; FORMALIN-INDUCED NOCICEPTION; EXCITATORY AMINO-ACIDS; MESSENGER-RNA; MECHANICAL HYPERALGESIA; PERIAQUEDUCTAL GRAY; VAGAL MODULATION; INDUCED RELEASE; SPINAL-CORD; VMH LESION AB The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception. These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control an ongoing vagus-mediated adjustment in the organism's nociceptive sensitivity. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, Room C-522,Campus Box 0440, San Francisco, CA 94143 USA. RI Green, Paul/C-5943-2011 FU NINR NIH HHS [NR04880] NR 54 TC 8 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 119 IS 1 BP 215 EP 221 DI 10.1016/S0306-4522(03)00136-2 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 688DN UT WOS:000183418000021 PM 12763082 ER PT J AU Jones, S Yakel, JL AF Jones, S Yakel, JL TI Casein kinase II (protein kinase CK2) regulates serotonin 5-HT3 receptor channel function in NG108-15 cells SO NEUROSCIENCE LA English DT Article DE serotonin receptors; patch-clamp; phosphorylation; plasticity; neuromodulation; desensitization ID GATED ION CHANNELS; HIPPOCAMPAL INTERNEURONS; RAT; PHOSPHORYLATION; ACTIVATION; RESPONSES; DESENSITIZATION; POTENTIATION; INDUCTION; SYSTEM AB We have used whole-cell recording techniques in the mouse neuroblastoma X rat glioma hybrid NG108-15 cell line to test whether protein kinase CK2 (CK2; also known as casein kinase II) modulates the function of the serotonin 5-HT3 receptor (5-HT3R) channel. The rapid application of 5-HT (50 muM) to NG108-15 cells elicits a 5-HT3R-mediated inward current response that rapidly reaches peak amplitude and then desensitizes in the continued presence of agonist. Internal dialysis with CK2 (20 mug/ml) via the patch pipette significantly increases the amplitude and decreases the rate of desensitization of the 5-HT3R-mediated responses. CK2 that had been heat-inactivated has no effect on either the amplitude or the kinetics of desensitization of the 5-HT3R responses. These data suggest that dialysis with protein kinase CK2 significantly enhanced current through the 5-HT3R channel, and that CK2 may be an important regulator of 5-HT3R channel function in the nervous system, possibly serving to facilitate the 5-HT-induced excitation of the cells. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. NR 28 TC 14 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 119 IS 3 BP 629 EP 634 DI 10.1016/S0306-4522(03)00202-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 694CF UT WOS:000183755700002 PM 12809683 ER PT J AU Miao, FJP Janig, W Jasmin, L Levine, JD AF Miao, FJP Janig, W Jasmin, L Levine, JD TI Blockade of nociceptive inhibition of plasma extravasation by opioid stimulation of the periaqueductal gray and its interaction with vagus-induced inhibition in the rat SO NEUROSCIENCE LA English DT Article DE neurogenic inflammation; nociceptive afferents; vagus afferents; periaqueductal gray; descending antinociception; adrenal medulla ID FEEDBACK NEUROENDOCRINE CONTROL; MECHANICAL HYPERALGESIA; INFLAMMATORY RESPONSE; INTRATHECAL NICOTINE; VAGAL MODULATION; BRADYKININ; MORPHINE; NEURONS; MEDULLA AB We have previously shown that stimulation of cutaneous or visceral nociceptors suppresses inflammation measured as bradykinin-induced synovial plasma extravasation in the knee joint of the rat. This suppression occurs through the activation of a spinal as well as a supraspinal reflex pathway leading to activation of the adrenal medullae and probably the release of epinephrine. These nociceptive-neuroendocrine reflex pathways are tonically inhibited by activity in abdominal vagal afferents acting through an inhibitory descending pathway projecting through the dorsolateral funiculus (DLF) ipsilateral to the cutaneous afferent nociceptive input. Here we investigated whether the descending inhibitory pathway acted upon by vagal afferents is also modulated by the periaqueductal gray (PAG), similar to other bulbo-spinal pathways acting on spinal nociceptive transmission. Injection of morphine sulfate (10 nmol) in the ventrolateral PAG significantly inhibited the nociceptive-neuroendocrine reflex pathways, an effect that was significantly less after removal of vagal afferents (i.e. after release from tonic inhibition maintained by vagal afferents). Interruption of the DLF ipsilateral to the nociceptive input removed the inhibitory effect of vagal afferents and partly reduced the inhibition produced by morphine injected in the PAG. From these investigations we conclude that PAG-induced inhibition of the nociceptive-neuroendocrine reflex pathways is mediated through the DLF ipsilateral to the nociceptive input, involving the same descending inhibitory pathway that relays afferent vagal inhibition, and through other spinal and possibly supraspinal pathways. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Calif San Francisco, Dept Med, NIH Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol Surg & Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Kiel, Inst Physiol, D-24098 Kiel, Germany. RP Levine, JD (reprint author), Univ Calif San Francisco, Dept Med, NIH Pain Ctr, Box 0440, San Francisco, CA 94143 USA. NR 27 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 119 IS 3 BP 875 EP 885 DI 10.1016/S0306-4522(03)00106-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 694CF UT WOS:000183755700026 PM 12809707 ER PT J AU Kiyatkin, EA Mitchum, RD AF Kiyatkin, EA Mitchum, RD TI Fluctuations in brain temperature during sexual interaction in male rats: An approach for evaluating neural activity underlying motivated behavior SO NEUROSCIENCE LA English DT Article DE nucleus accumbens; medical-preoptic hypothalamus; neural activation; arousal; motivation; reward ID FREELY MOVING ANIMALS; BASAL GANGLIA; PREOPTIC AREA; HEART-RATE; AROUSAL; STIMULATION; POTENTIALS; DOPAMINE; NEURONS AB Since metabolic activity is accompanied by heat release, measurement of brain temperatures offers a method for assessing behavior-associated changes in neural activity. To explore this possibility, we monitored local brain (nucleus accumbens, medial-preoptic hypothalamus, and hippocampus) and body (temporal muscle) temperature in an experienced male rat during sexual behavior with a sexually receptive female. Placement of the female into a neighboring compartment increased the male's temperature and additional increases occurred when rats were allowed to see and partially interact with the female through a Plexiglas barrier with dime-size holes. The temperature increase was robust (1.5-2.0 degreesC), faster in all brain areas than in muscle, and peaked (38-39 degreesC) when the barrier was removed and full interaction was allowed. As the male repeatedly mounted and achieved intromission with the female, temperature further increased, peaking at ejaculation (+0.2-0.4 degreesC). Following ejaculation, the temperature abruptly dropped, until sexual interest and interaction resumed. These biphasic temperature fluctuations were generally similar in each recording location, but all brain sites (particularly, nucleus accumbens and medial-preoptic hypothalamus) showed more profound changes than the muscle. These data generally match single-unit and other physiological findings, suggesting that male sexual behavior is accompanied by sustained and generalized neural activation. This activation is triggered by sexually relevant stimuli (arousal), maintained during repeated mounts and intromissions, and peaked at ejaculation. These findings suggest brain temperature fluctuations not only as a sensitive index of functional neural activation, but as a powerful factor affecting various neural functions and an important part of brain mechanisms underlying motivated behavior. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 47 TC 30 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 119 IS 4 BP 1169 EP 1183 DI 10.1016/S0306-4522(03)00222-7 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 700HT UT WOS:000184107100021 PM 12831871 ER PT J AU Ma, W Li, BS Maric, D Zhao, WQ Lin, HJ Zhang, L Pant, HC Barker, JL AF Ma, W Li, BS Maric, D Zhao, WQ Lin, HJ Zhang, L Pant, HC Barker, JL TI Ethanol blocks both basic fibroblast growth factor- and carbachol-mediated neuroepithelial cell expansion with differential effects on carbachol-activated signaling pathways SO NEUROSCIENCE LA English DT Article DE neural precursor cells; muscarinic acetylcholine receptors; proliferation; apoptosis; protein phosphorylation; Ca2+ signaling ID PHEOCHROMOCYTOMA PC12 CELLS; FETAL ALCOHOL SYNDROME; PROTEIN-KINASE-C; MUSCARINIC RECEPTORS; PROGENITOR CELLS; ASTROGLIAL CELLS; BINDING PROTEIN; CEREBRAL-CORTEX; CYCLE KINETICS; DNA-SYNTHESIS AB We have expanded neuroepithelial cells dissociated from the embryonic rat telencephalon in serum-free defined medium containing basic fibroblast growth factor (bFGF) in order to generate a model neuroepithelium to study the interaction of ethanol with both growth factor- and transmitter-stimulated proliferation. Ethanol blocked proliferation stimulated by bFGF and by carbachol, an agonist at muscarinic acetylcholine receptors, in a dose-dependent manner. In addition, ethanol attenuated autonomous expansion of neuroepithelial cells occurring following withdrawal of bFGF. The latter effect was associated with an increase in the number of apoptotic cells identified by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling labeling. We studied the effects of ethanol on carbachol-stimulated signaling pathways critical to its proliferative effects. Ethanol significantly reduced carbachol-stimulated Ca2+ signaling, as well as Erk1/Erk2, Akt and cyclic AMP-response element-binding phosphorylations in a dose-dependent manner. Comparison of the potency of ethanol in attenuating carbachol-stimulated proliferation and signal transduction showed that mitogen-activated protein kinase phosphorylation was less sensitive to ethanol than the other parameters. The results indicate that ethanol's suppression of proliferation induced by carbachol in this model neuroepithelium likely involves multiple signaling pathways. These effects in vitro may help to explain the devastating effects of prenatal ethanol exposure in vivo, which contribute to the fetal alcohol syndrome. (C) 2003 Published by Elsevier Science Ltd on behalf of IBRO. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. RP Ma, W (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, 4555 Overlook Ave SW, Washington, DC 20375 USA. NR 37 TC 17 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 118 IS 1 BP 37 EP 47 DI 10.1016/S0306-4522(02)00812-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 669MJ UT WOS:000182354800006 PM 12676135 ER PT J AU Yang, HYT Iadarola, MJ AF Yang, HYT Iadarola, MJ TI Activation of spinal neuropeptide FF and the neuropeptide FF receptor 2 during inflammatory hyperalgesia in rats SO NEUROSCIENCE LA English DT Article DE nociception; pain; inflammation; dorsal spinal; cord; NPVF ID MORPHINE-MODULATING PEPTIDES; CENTRAL-NERVOUS-SYSTEM; CARRAGEENAN INFLAMMATION; MAMMALIAN NEUROPEPTIDE; FMRF-NH2-LIKE PEPTIDE; VASOPRESSIN RELEASE; CONSCIOUS RATS; CORD; PAIN; FLFQPQRFAMIDE AB Several lines of evidence suggest that neuropeptide FF (NPFF) is involved in nociception and in the modulation of opioid-mediated analgesia. Following the identification of the precursor protein for NPFF, two NPFF receptors and a second PQRF-NH2 containing peptide, termed NPVF, were identified. To further explore the functional role of PQRF-NH2 peptides, we have studied their distribution and also the regulation of NPFF and NPVF systems in the spinal cord of rats with peripheral inflammation. The distribution of NPFF gene expression is very similar to that of NPFF immunoreactive peptide but is distinct from NPVF gene expression. In the rat spinal cord, gene expression of NPFF but not that of NPVF was up-regulated by persistent pain induced by carrageenan inflammation. The distribution of NPFF receptor 2 gene expression is very similar to that of the NPFF peptide with a striking localization in the superficial layer of spinal cord. In rats with carrageenan inflammation of the hind paw, expression of both NPFF and NPFF receptor 2 genes was up-regulated in the spinal cord, while expression of NPVF and NPFF receptor 1 genes was not affected. The results of this study demonstrate a coordinated involvement of the spinal NPFF system in the persistent nociceptive pain states. Several studies have found a potentiation and prolongation of morphine analgesia by NPFF, therefore, it is highly possible that the endogenous spinal NPFF system contributes to the enhanced analgesic potency of morphine in animals with peripheral inflammation. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIDCR, Neuronal Gene Expres Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Yang, HYT (reprint author), NIDCR, Neuronal Gene Expres Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bldg 49,Room 1A07,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. NR 39 TC 27 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 118 IS 1 BP 179 EP 187 DI 10.1016/S0306-4522(02)00931-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 669MJ UT WOS:000182354800019 PM 12676148 ER PT J AU Tanner, KD Reichling, DB Gear, RW Paul, SM Levine, JD AF Tanner, KD Reichling, DB Gear, RW Paul, SM Levine, JD TI Altered temporal pattern of evoked afferent activity in a rat model of vincristine-induced painful peripheral neuropathy SO NEUROSCIENCE LA English DT Article DE vincristine; cancer; plasticity; chemotherapy; sensory nerve; neuropathic pain ID NOXIOUS MECHANICAL STIMULATION; C-FIBER NOCICEPTORS; VENTRAL SPINAL-CORD; NEURONS IN-VITRO; SUBSTANCE-P; ELECTRICAL-STIMULATION; DIFFERENTIAL RELEASE; SENSORY NEURONS; SENSITIZATION; SENSATIONS AB It is known that the level of activity in nociceptive primary afferent nerve fibers increases in neuropathic conditions that produce pain, but changes in the temporal patterning of action potentials have not been analyzed in any detail. Because the patterning of action potentials in sensory nerve fibers might play a role in the development of pathological pain states, we studied patterning of mechanical stimulus-evoked action potential trains in nociceptive primary afferents in a rat model of vincristine-induced painful peripheral neuropathy. Systemic administration of vincristine (100 mug/kg) caused approximately half the C-fiber nociceptors to become markedly hyperresponsive to mechanical stimulation. Instantaneous frequency plots showed that vincristine induced an irregular pattern of action-potential firing in hyperresponsive C-fibers, characterized by interspersed occurrences of high- and low-frequency firing. This pattern was associated with an increase in the percentage of interspike intervals 100-199 ms in duration compared with that in C-fibers from control rats and vincristine-treated C-fibers that did not become hyperresponsive. Variability in the temporal pattern of action potential firing was quantified by determining the coefficient of variability (CV2) for adjacent interspike intervals. This analysis revealed that vincristine altered the pattern of action-potential timing, so that combinations of higher firing frequency and higher variability occurred that were not observed in control fibers. The abnormal temporal structure of nociceptor responses induced by vincristine in some C-fiber nociceptors could contribute to the pathogenesis of chemotherapy-induced neuropathic pain, perhaps by inducing activity-dependent post-synaptic effects in sensory pathways. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Calif San Francisco, NIH Pain Ctr, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Program Neurosci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, Dept Oral & Maxillofacial Surg, Room C-555,Campus Box 0440, San Francisco, CA 94143 USA. FU NIDCR NIH HHS [DE 08973]; NINDS NIH HHS [NS 21647] NR 52 TC 29 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 118 IS 3 BP 809 EP 817 DI 10.1016/S0306-4522(03)00023-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA 673YW UT WOS:000182609700020 PM 12710988 ER PT J AU Zohar, O Schreiber, S Getslev, V Schwartz, JP Mullins, PG Pick, CG AF Zohar, O Schreiber, S Getslev, V Schwartz, JP Mullins, PG Pick, CG TI Closed-head minimal traumatic brain injury produces long-term cognitive deficits in mice SO NEUROSCIENCE LA English DT Article DE time course; force dependent; learning rate; Morris water maze; memory; minimal traumatic brain injury (mTBI); animal model ID CONTROLLED CORTICAL IMPACT; SELECTIVE VULNERABILITY; PERFORMANCE; RATS; HIPPOCAMPUS; ISCHEMIA; MODELS; DAMAGE AB Victims of minimal traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study we adopted a non-invasive closed-head weight-drop mouse model to produce mTBI. We examined the effects of 20,25, or 30 g weight drop 7, 30, 60 and 90 days following injury on mice's ability to perform the Morris water maze. The mice suffered profound long-lasting learning and memory deficits that were force- and time-dependent. Although the injured mice could acquire the task, they could not improve their initial escape latency by more than 50%, while normal mice improved by up to 450% (P<0.001). In order to directly compare the learning ability of individual mice following our mTBI we have devised a new measure which we term learning rate. We define learning rate as the rate the mouse improved its own performance in consecutive trials in a given experimental day. The learning rate of control mice increased linearly throughout the testing period with a slope of approximately 0.9. Injured mice that sustained 20 and 25 g weight drop could also improve their learning rate linearly but with a slope of only 0.2. Mice who sustained 30 g weight drop could not improve their learning rate linearly and reached a plateau after the third experimental learning day. These results indicate that the severity of injury may correlate with the degree of integration of the learning task. These cognitive deficits occurred without any other clear neurological damage, no evident brain edema, no notable damage to the blood-brain barrier and no early anatomical changes to the brain (observed by magnetic resonance imaging imaging). These results demonstrate that persistent deficits of cognitive learning abilities in mice, similar to those observed in human post-concussive syndrome, can follow mTBI without any anatomical damage to the brain and its surrounding tissue. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. Tel Aviv Sourasky Med Ctr, Dept Psychiat, IL-69978 Tel Aviv, Israel. NINDS, Neurotroph Factors Sect, NIH, Bethesda, MD 20892 USA. Univ New Mexico, Clin Magnet Resonance Res Ctr, Albuquerque, NM 87131 USA. RP Pick, CG (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. RI Schreiber, Shaul/E-5821-2010; Pick, Chaim/D-4789-2009; OI Schreiber, Shaul/0000-0002-2189-0693; Mullins, Paul/0000-0002-1339-6361 NR 32 TC 102 Z9 110 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 118 IS 4 BP 949 EP 955 DI 10.1016/S0306-4522(03)00048-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 679MT UT WOS:000182926900007 PM 12732240 ER PT J AU Hashimoto, R Senatorov, V Kanai, H Leeds, P Chuang, DM AF Hashimoto, R Senatorov, V Kanai, H Leeds, P Chuang, DM TI Lithium stimulates progenitor proliferation in cultured brain neurons SO NEUROSCIENCE LA English DT Article DE cerebellar granule cells; cerebral cortical neurons; glutamate; glucocorticold; haloperidol; neurogenesis ID SYNTHASE KINASE 3-BETA; RAT DENTATE GYRUS; CELL-PROLIFERATION; ADULT NEUROGENESIS; IN-VITRO; RECEPTOR; INHIBITION; PHOSPHORYLATION; EXCITOTOXICITY; INVOLVEMENT AB The number of neurons in the brain is controlled by production of new neurons and neuronal death. Neural progenitor proliferation in the developing and adult brain plays a prominent role in the production of new neurons. Here, we examined the effects of lithium, a mood-stabilizing drug, on neuronal proliferation in rat primary neuronal cultures. The incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating DNA was used to label proliferating cells. BrdU incorporation was detected by immunocytochemistry in cerebellar granule cells prepared from postnatal rats and cerebral cortical cultures prepared from embryonic rats. Quantification of BrdU incorporation into cultures was performed by counting BrdU-positive cells and BrdU-coupled enzyme-linked immunosorbent assay. Both methods revealed that lithium increased BrdU incorporation in cerebellar granule cells and cerebral cortical cultures. Most BrdU-positive cells colocalized with nestin, a neuroblast cell marker, in cerebral cortical cultures. Blockade of DNA replication by cytosine arabinoside almost completely abolished BrdU incorporation, suggesting that lithium-induced BrdU incorporation was mainly due to enhanced DNA replication. Glutamate, glucocorticoids and haloperidol were found to markedly reduce neural progenitor proliferation in cerebellar granule cells. The presence of lithium prevented the loss of proliferation induced by these agents. Lithium-induced neural progenitor proliferation in vitro suggests that similar effects might occur in vivo and this action could also be related to its clinical efficacy. Cultured brain neurons may provide a valuable model for studying the molecular mechanisms underlying lithium-induced up-regulation of neural proliferation. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIMH, Mol Neurobiol Sect, Mood Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RI Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 NR 35 TC 70 Z9 75 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 117 IS 1 BP 55 EP 61 DI 10.1016/S0306-4522(02)00577-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 653AA UT WOS:000181412000007 PM 12605892 ER PT J AU Blakeman, KH Hao, JX Xu, XJ Jacoby, AS Shine, J Crawley, JN Iismaa, T Wiesenfeld-Hallin, Z AF Blakeman, KH Hao, JX Xu, XJ Jacoby, AS Shine, J Crawley, JN Iismaa, T Wiesenfeld-Hallin, Z TI Hyperalgesia and increased neuropathic pain-like response in mice lacking galanin receptor 1 receptors SO NEUROSCIENCE LA English DT Article DE antinociception; neuropathy; pain; spinal cord ID PERIPHERAL-NERVE INJURY; ROOT GANGLION-CELLS; SPINAL-CORD; INTRATHECAL GALANIN; SCIATIC-NERVE; SENSORY NEURONS; FLEXOR REFLEX; RAT; MONONEUROPATHY; RELEASE AB The neuropeptide galanin may have a role in modulation of nociception, particularly after peripheral nerve injury. The effect of galanin is mediated by at least three subtypes of receptors. In the present study, we assessed the nociceptive sensitivity in mice lacking the galanin receptor 1 gene (Galr1) and the development of neuropathic pain-like behaviours after photochemically induced partial sciatic nerve ischaemic injury. Under basal condition, Galr1 knockout (Galr1(-/-)) mice had shortened response latency on the hot plate, but not tail flick and paw radiant heat, tests. The mechanical sensitivity was not different between Galr1(-/-) and wild type (Galr1(+/+)) mice, whereas the cold response was moderately enhanced in Galr1(-/-) mice. Both Galr1(-/-) mice and Galr1(+/+) controls developed mechanical and heat hypersensitivity after partial sciatic nerve injury. The duration of such pain-like behaviours was significantly increased in Galr1(-/-). The Galr1(-/-) mice and Galr1(+/+) mice did not differ in their recovery from deficits in toe-spread after sciatic nerve crush. The results provide some evidence for an inhibitory function for the neuropeptide galanin acting on galanin receptor 1 (GALR1) in nociception and neuropathic pain after peripheral nerve injury in mice. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Huddinge Univ Hosp, Karolinska Inst, Div Clin Neurophysiol, Dept Med Lab Sci & Technol, Stockholm, Sweden. NIMH, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. Garvan Inst Med Res, Neurobiol Program, Sydney, NSW, Australia. RP Wiesenfeld-Hallin, Z (reprint author), Huddinge Univ Hosp, Karolinska Inst, Div Clin Neurophysiol, Dept Med Lab Sci & Technol, Stockholm, Sweden. EM zsuzsanna.wiesenfeld-hallin@neurophys.hs.sll.se NR 32 TC 59 Z9 61 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 117 IS 1 BP 221 EP 227 DI 10.1016/S0306-4522(02)00779-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 653AA UT WOS:000181412000023 PM 12605908 ER PT J AU Yunker, AMR Sharp, AH Sundarraj, S Ranganathan, V Copeland, TD McEnery, MW AF Yunker, AMR Sharp, AH Sundarraj, S Ranganathan, V Copeland, TD McEnery, MW TI Immunological characterization of T-type voltage-dependent calcium channel Ca(V)3.1 (alpha1G) and Ca(V)3.3 (alpha1l) isoforms reveal differences in their localization, expression, and neural development SO NEUROSCIENCE LA English DT Article DE T-type calcium channel; anti-peptide antibody; cerebellum; hippocampus; olfactory bulb ID CENTRAL-NERVOUS-SYSTEM; SUBUNIT MESSENGER-RNA; CA2+ CHANNELS; RAT-BRAIN; FUNCTIONAL-CHARACTERIZATION; ALPHA(1G) SUBUNIT; GATING PROPERTIES; THALAMIC NEURONS; ABSENCE EPILEPSY; BETA-SUBUNITS AB Low voltage-activated calcium channels (LVAs; "T-type") modulate normal neuronal electrophysiological properties such as neuronal pacemaker activity and rebound burst firing, and may be important anti-epileptic targets. Proteomic analyses of available alpha1G/Ca(V)3.1 and alpha1I/Ca(V)3.3 sequences suggest numerous potential isoforms, with specific alpha1G/Ca(V)3.1 or alpha1I/Cav3.3 domains postulated to be conserved among isoforms of each T-type channel subtype. This information was used to generate affinity-purified anti-peptide antibodies against sequences unique to alpha1G/Ca(V)3.1 or alpha1I/Cav3.3, and these antibodies were used to compare and contrast alpha1G/Ca(V)3.1 and alpha1I/Cav3.3 protein expression by western blotting and immunohistochemistry. Each antibody reacted with appropriately sized recombinant protein in HEK-293 cells. Regional and developmental differences in alpha1G/Ca(V)3.1 and alpha1I/Cav3.3 protein expression were observed when the antibodies were used to probe regional brain dissections prepared from perinatal mice and adult rodents and humans. Mouse forebrain alpha1G/Ca(V)3.1 (similar to240 kDa) was smaller than cerebellar (similar to260 kDa) alpha1G/Ca(V)3.1, and expression of both proteins increased during perinatal development. In contrast, mouse midbrain and diencephalic tissues evidenced an alpha1I/Ca(V)3.3 immunoreactive doublet (similar to230 kDa and similar to190 kDa), whereas other brain regions only expressed the small alpha1I/Cav3.3 isoform. A unique large alpha1I/Cav3.3 isoform (similar to260 kDa) was expressed at birth and eventually decreased, concomitant with the appearance and gradual increase of the small alpha1I/Ca(V)3.3 isoform. Immunohistochemistry supported the conclusion that LVAs are expressed in a regional manner, as cerebellum strongly expressed alpha1G/Ca(V)3.1, and olfactory bulb and midbrain contained robust alpha1I/Ca(V)3.3 immunoreactivity. Finally, strong alpha1I/Ca(V)3.3, but not alpha1G/Ca(V)3.1, immunoreactivity was observed in brain and spinal cord by embryonic day 14 in situ. Taken together, these data provide an anatomical and biochemical basis for interpreting LVA heterogeneity and offer evidence of developmental regulation of LVA isoform expression. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Case Western Reserve Univ, Sch Med, Dept Gen Med Sci, Cleveland, OH 44106 USA. NCI, Basic Res Lab, Frederick, MD 21702 USA. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Phys, Cleveland, OH 44106 USA. RP McEnery, MW (reprint author), Case Western Reserve Univ, Sch Med, Dept Gen Med Sci, E699,10900 Euclid Ave, Cleveland, OH 44106 USA. FU NIMH NIH HHS [MH55747] NR 60 TC 49 Z9 49 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 117 IS 2 BP 321 EP 335 DI 10.1016/S0306-4522(02)00936-3 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 656AD UT WOS:000181585500007 PM 12614673 ER PT J AU Ruskin, DN Bergstrom, DA Tierney, PL Walters, JR AF Ruskin, DN Bergstrom, DA Tierney, PL Walters, JR TI Correlated multisecond oscillations in firing rate in the basal ganglia: Modulation by dopamine and the subthalamic nucleus SO NEUROSCIENCE LA English DT Article DE apomorphine; phase relationship; ultraslow oscillations; synchrony; globus pallidus; substantia nigra pars reticulata ID PARS-RETICULATA NEURONS; GLOBUS-PALLIDUS; SUBSTANTIA-NIGRA; CEREBRAL HEMODYNAMICS; CA2+ OSCILLATIONS; RECEPTOR AGONISTS; D-AMPHETAMINE; HUMAN BRAIN; IN-VIVO; APOMORPHINE AB Previous studies from this laboratory have shown that many neurons in the basal ganglia have multisecond (<0.5 Hz) periodicities in firing rate in awake rats. The frequency and regularity of these oscillations are significantly increased by systemically injected dopamine (DA) agonists. Because oscillatory activity should have greater functional impact if shared by many neurons, the level of correlation of multisecond oscillations was assessed by recording pairs of neurons in the globus pallidus and substantia nigra pars reticulata in the same hemisphere, or pairs of globus pallidus neurons in opposite hemispheres in awake, immobilized rats. Cross-correlation (90-180 s lags) and spectral analysis were used to characterize correlated oscillations. Thirty-eight percent of pairs recorded in baseline (n=50) demonstrated correlated multisecond oscillations. Phase relationships were near 0 or 180degrees. DA agonist injection significantly increased the incidence of correlation (intra- and interhemispheric) to 94% (n=17). After DA agonist injection, phase relationships of globus pallidus/substantia nigra neuron pairs were exclusively concentrated near 180, and phases of interhemispheric pairs of globus pallidus neurons were concentrated near 0degrees. After subthalamic nucleus lesion (n=8), the incidence of correlated multisecond oscillations (or of multisecond oscillations per se) was not changed, although the consistent phase relationship between the globus pallidus and substantia nigra pars reticulata was disrupted. Subthalamic lesion also blocked apomorphine-induced decreases in oscillatory period and increases in oscillation amplitude, and significantly attenuated apomorphine-induced changes in mean firing rate. The data demonstrate that multisecond oscillations in the basal ganglia can be correlated between nuclei, and that DA receptor activation increases the level of correlation and organizes internuclear phase relationships at these multisecond time scales. While the subthalamic nucleus is not necessary for generating or transmitting these slow oscillations, it is involved in DA agonist-induced modulation of mean firing rate, oscillatory period, and internuclear phase relationship. These data further support a role for DA in modulating coherent oscillatory activity in the basal ganglia, and for the subthalamic nucleus in shaping the effects of DA receptor stimulation on basal ganglia output. Published by Elsevier Science Ltd on behalf of IBRO. C1 NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, 10 Ctr Dr,MSC 1406,Bldg 10 Room 5C103, Bethesda, MD 20892 USA. RI Tierney, Patrick/E-5860-2010 NR 71 TC 37 Z9 39 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 117 IS 2 BP 427 EP 438 DI 10.1016/S0306-4522(02)00921-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 656AD UT WOS:000181585500017 PM 12614683 ER PT J AU Matsumoto, M Weickert, CS Akil, M Lipska, BK Hyde, TM Herman, MM Kleinman, JE Weinberger, DR AF Matsumoto, M Weickert, CS Akil, M Lipska, BK Hyde, TM Herman, MM Kleinman, JE Weinberger, DR TI Catechol O-methyltransferase mRNA expression in human and rat brain: Evidence for a role in cortical neuronal function SO NEUROSCIENCE LA English DT Article DE dopamine; functional polymorphism; prefrontal cortex; striatum; midbrain schizophrenia ID MEDIAL PREFRONTAL CORTEX; WORKING-MEMORY DEFICITS; DOPAMINE D1 RECEPTORS; MONOAMINE-OXIDASE; CEREBRAL-CORTEX; SCHIZOPHRENIA; LOCALIZATION; TRANSPORTER; COMT; ENZYME AB Catechol O-methyltransferase (COMT) is involved in the inactivation of catecholamines, including the neurotransmitter dopamine. A Val(108/158) Met functional polymorphism of the COMT gene has been shown to affect working memory-associated frontal lobe function in humans. In the present study, in situ hybridization histochemistry was employed to determine the mRNA expression profile of COMT in the human prefrontal cortex, striatum and midbrain and in the rat forebrain. In both species, COMT mRNA signals were observed in large pyramidal and smaller neurons in all cortical layers of the prefrontal cortex as well as in medium and large neurons in the striatum. Levels of COMT mRNA were obviously higher in neurons than in glia. The striatum, which receives a dense dopaminergic input, expressed lower levels of COMT mRNA as compared with the prefrontal cortex. Consistent with previous protein expression data, COMT mRNA was abundant in ependymal cells lining the cerebral ventricles. In the midbrain, COMT mRNA was detected in dopaminergic neurons in both species, albeit at low levels. In the rat forebrain, dense labeling was also detected in choroid plexus and hippocampal dentate gyrus and Ammon's horn neurons. Contrary to expectations that COMT would be expressed predominantly in non-neuronal cells, the present study shows that neurons are the main cell populations expressing COMT mRNA in the prefrontal cortex and striatum. Combined with previous data about protein localization, the present results suggest that the membrane-bound isoform of COMT having a high affinity for dopamine is expressed at neuronal dendritic processes in human cortex, consistent with functional evidence that it plays an important role in dopaminergic neurotransmission. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Matsumoto, M (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr 4N312, Bethesda, MD 20892 USA. RI Shannon Weickert, Cynthia/G-3171-2011; Matsumoto, Mitsuyuki/G-3207-2012; Lipska, Barbara/E-4569-2017 OI Matsumoto, Mitsuyuki/0000-0002-1172-2354; NR 70 TC 207 Z9 210 U1 4 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 116 IS 1 BP 127 EP 137 AR PII S0306-4522(02)00556-0 DI 10.1016/S0306-4522(02)00556-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 641GX UT WOS:000180738000017 PM 12535946 ER PT J AU Sarabi, A Hoffer, BJ Olson, L Morales, M AF Sarabi, A Hoffer, BJ Olson, L Morales, M TI Glial cell line neurotrophic factor-family receptor alpha-1 is present in central neurons with distinct phenotypes SO NEUROSCIENCE LA English DT Article DE glial cell line neurotrophic factor; interneurons; glutamic acid decarboxylase; serotonin and septum ID MIDBRAIN DOPAMINERGIC-NEURONS; NITRIC-OXIDE SYNTHASE; C-RET PROTOONCOGENE; NERVE GROWTH-FACTOR; MICE LACKING GDNF; IN-VIVO; MESSENGER-RNAS; HIPPOCAMPAL INTERNEURONS; PARKINSONS-DISEASE; TYROSINE KINASE AB Glial cell line neurotrophic factor(GDNF) is a potent survival factor for several types of neurons. GDNF binds with high affinity to the GDNF-family receptor alpha-1 (GFRalpha-1) which is expressed in different brain areas. In the present study, by using anatomical techniques, we document the phenotypic diversity among GFRalpha-1 expressing neurons in the CNS. GFRalpha-1 expression was found in GABA (gamma-aminobutyric acid)-containing neurons distributed in the cortex, reticular thalamic nucleus and septum. While high expression of GFRalpha-1 was often observed in cholinergic motoneurons in the spinal cord, very few septal cholinergic neurons were found to express GFRalpha-1. GFRalpha-1 transcripts were also detected in catecholaminergic neurons in the periventricular hypothalamic nucleus, dorsal raphe nucleus and locus ceruleus. Within the raphe nucleus, GFRalpha-1 expression was prominent in many serotonergic neurons and in few neurons containing the enzyme nitric oxide synthase. As GFRalpha-1 is activated by GDNF and GDNF-related neurotrophic factors, the widespread distribution of GFRalpha-1 in neurons with different phenotypes indicates that the neuronal activity of these neurons is likely to be affected by GDNF and GDNF-related neurotrophic factors. This would result in the regulation of diverse neuronal pathways in the adult brain. Published by Elsevier Science Ltd on behalf of IBRO. C1 Natl Inst Drug Abuse, Cellular Neurophysiol Sect, Baltimore, MD 21224 USA. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. RP Morales, M (reprint author), Natl Inst Drug Abuse, Cellular Neurophysiol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 51 TC 14 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 116 IS 1 BP 261 EP 273 AR PII S0306-4522(02)00559-6 DI 10.1016/S0306-4522(02)00559-6 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 641GX UT WOS:000180738000029 PM 12535958 ER PT J AU Schmidt, ED Aguilera, G Binnekade, R Tilders, FJH AF Schmidt, ED Aguilera, G Binnekade, R Tilders, FJH TI Single administration of interleukin-1 increased corticotropin releasing hormone and corticotropin releasing hormone-receptor mRNA in the hypothalamic arav ntricular nucl us which paralleled long-lasting (weeks) sensitization to emotional stressors SO NEUROSCIENCE LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; PITUITARY-ADRENAL AXIS; VASOPRESSIN V1B RECEPTOR; NECROSIS-FACTOR-ALPHA; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; C-FOS; DIFFERENTIAL REGULATION; IMMOBILIZATION STRESS; ARGININE-VASOPRESSIN AB Single exposure to the proinflammatory cytokine interleukin-1 induces sensitization of the adrenocorticotropin hormone and corticosterone responses to stressors weeks later (hypothalamus-pituitary-adrenal sensitization). Hypothalamus-pituitary-adrenal responses are controlled by corticotropin-releasing hormone and arginine-vasopressin secreted from parvocellular corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus and may involve autoexcitatory feedback mechanisms. Therefore, we studied the temporal relationship between resting levels of corticotropin-releasing hormone, corticotropin-releasing hormone-R1 and arginine-vasopressin receptor (V1a, V1b) mRNAs in the paraventricular nucleus and the development of hypothalamus-pituitary-adrenal sensitization to an emotional stressor (novelty). The adrenocorticotropin hormone precursor molecule proopiomelanocortin hnRNA in the pituitary gland served as an index for acute activation. Single administration of interleukin-1 induced sensitization of the hypothalamus-pituitary-adrenal to novelty from 3 to 22 days later, but not after 42 days. Single administration of interleukin-1 induced biphasic increases in corticotropin-releasing hormone and corticotropin-releasing hormone-R1 mRNAs in the paraventricular nucleus: an early peak within 24 h, followed by a delayed (>7 days) increase that peaked after 22 days. Hypothalamic V1a and V1b mRNA levels were unaffected. In contrast, in the pituitary gland, there was an early decrease in corticotropin-releasing hormone-R1 mRNA (from 10.5 to 3 h after interleukin-1) and V1b receptor mRNA (3 to 6 h), which returned to control levels from 24 h onwards. Thus, interleukin-1-induced long-lasting hypothalamus-pituitary-adrenal sensitizationis associated with prolonged activation of corticotropin-releasing hormone and corticotropin-releasing hormone-R1 mRNA expression in the paraventricular nucleus, but not with changes in the expression of proopiomelanocortin hnRNA or V1b receptor or corticotropin-releasing hormone R1 mRNAs in the pituitary gland. We propose that transient exposure to immune events can induce long-lasting hypothalamus-pituitary-adrenal sensitization, which at least in part involves long-term hypothalamic adaptations that enhance central corticotropin-releasing hormone signaling. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Vrije Univ Amsterdam, Grad Sch Neurosci Amsterdam, Neurosci Res Inst, NL-1081 BT Amsterdam, Netherlands. Natl Inst Hlth, Sect Endocrine Physiol, Bethesda, MD USA. RP Schmidt, ED (reprint author), Vrije Univ Amsterdam, Grad Sch Neurosci Amsterdam, Neurosci Res Inst, Van Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM ed.schmidt.pharm@med.vu.nl NR 81 TC 55 Z9 58 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 116 IS 1 BP 275 EP 283 AR PII S0306-4522(02)00555-9 DI 10.1016/S0306-4522(02)00555-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 641GX UT WOS:000180738000030 PM 12535959 ER PT J AU Kopnisky, KL Chalecka-Franaszek, E Gonzalez-Zulueta, M Chuang, DM AF Kopnisky, KL Chalecka-Franaszek, E Gonzalez-Zulueta, M Chuang, DM TI Chronic lithium treatment antagonizes glutamate-induced decrease of phosphorylated CREB in neurons via reducing protein phosphatase 1 and increasing MEK activities SO NEUROSCIENCE LA English DT Article DE lithium; glutamate; CREB; protein phosphatase; cerebellar granule cells; NMDA ID FAMILY TRANSCRIPTION FACTOR; CEREBELLAR GRANULE CELLS; LONG-TERM DEPRESSION; RAS-MAPK PATHWAY; NEUROTROPHIC FACTOR; GENE-TRANSCRIPTION; DEPENDENT MECHANISM; SIGNALING PATHWAY; BCL-2 EXPRESSION; CALCIUM INFLUX AB The cyclic AMP response element binding protein (CREB) has major roles in mediating adaptive responses at glutamatergic synapses and in the neuroprotective effects of neurotrophins. CREB has been implicated as a potential mediator of antidepressant actions. In vitro, chronic lithium treatment has been shown to promote neuronal cell survival. In the present study, we have used cultures of cerebellar granule neurons to analyze the effects of acute and chronic lithium treatment on the response to toxic concentrations of glutamate. Such concentrations of glutamate decrease the phosphorylation of CREB at serine(133) in an N-methyl-D-aspartate (NMDA) receptor-dependent manner. Chronic, but not acute, lithium treatment suppresses glutamate-induced decreases in phosphorylated CREB, and transfection studies indicate that chronic lithium, in the presence of a glutamate stimulus, markedly increases CRE-driven gene expression. Experiments with selected pharmacological reagents indicate that the glutamate-induced decreases in phosphorylated CREB are regulated primarily by protein phosphatase 1. Chronic lithium treatment not only decreases protein phosphatase 1 activity under these circumstances, but also augments glutamate-induced increases in MEK activity. PD 98059, a MEK inhibitor, prevents chronic lithium treatment from increasing phosphorylated CREB levels in glutamate-treated neurons. We conclude from these results that chronic lithium treatment is permissive for maintaining higher phosphorylated CREB levels in the presence of glutamate in part by decreasing protein phosphatase 1 activity and in part by increasing MEK activity. Higher levels of phosphorylated CREB and CRE-responsive genes such as bcl-2 may be responsible for lithium's reported effects on neuronal survival. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. AGY Therapeut Inc, San Francisco, CA 94080 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Ctr Dr,Room 4C206,MSC 1363, Bethesda, MD 20892 USA. NR 49 TC 62 Z9 65 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 116 IS 2 BP 425 EP 435 DI 10.1016/S0306-4522(02)00573-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 643MJ UT WOS:000180864800011 PM 12559097 ER PT J AU Kiyatkin, EA Brown, PL AF Kiyatkin, EA Brown, PL TI Fluctuations in neural activity during cocaine self-administration: Clues provided by brain thermorecording SO NEUROSCIENCE LA English DT Article DE brain temperature; neural activation; metabolism; drug-taking behavior; motivation; reward; rats ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; DOPAMINE UPTAKE; INTRAVENOUS COCAINE; MESOLIMBIC DOPAMINE; BEHAVING RATS; IN-VIVO; NEURONS; INHIBITION; STIMULI AB Since metabolic neural activity is accompanied by heat release, measurement of local brain temperature offers a method for assessing alterations in neural activity. This approach, continuous monitoring of local brain (ventral tegmental area, ventral striatum, and hippocampus) and body (temporal muscle) temperature, was used to study intravenous cocaine self-administration in trained rats. The first self-administration of a session was preceded by a strong temperature increase that continued after the drug infusion. After peaking at the time of the second self-administration, temperature plateaued (+0.7 degreesC) with biphasic fluctuations (+/-0.10-0.15 degreesC) around each subsequent self-administration. Temperature gradually increased before and for 30-50 s after the lever-press, but then abruptly decreased to a minimum at 180-240 s, when it began to increase to reach another peak immediately after the next lever-press. Doubling the dose of injected cocaine significantly potentiated the post-cocaine temperature decrease and increased time to the next lever-press. In contrast to drug-reinforced lever-presses, temperatures phasically increased after non-reinforced lever-presses and at the end of a session when the lever was blocked and the rat was hyperactive, trying to reach the inaccessible lever. While temperature changes in each recording location were generally correlative, the initial temperature elevation was stronger in all brain structures than in muscle and ventral striatum was the structure that showed the most pronounced and consistent temperature fluctuations. These data suggest a generalized brain activation associated with cocaine-seeking and cocaine-taking behavior with its phasic fluctuations around individual drug self-injections. While the initial component of brain activation preceding the first lever-press for cocaine is internally determined and closely related to behavioral search, subsequent biphasic fluctuations in neural activity associated with repeated drug intakes appear to be drug-mediated. Cocaine-induced potentiation of monoamine transmission is a possible factor for gradual increases in neural activity that drive cocaine seeking, while a rapid, brain concentration-dependent action on Na+ transport (local anesthetic action) is the most probable factor determining an abrupt, transient cessation of neural activation associated with cocaine reward. Published by Elsevier Science Ltd on behalf of IBRO. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 48 TC 29 Z9 29 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 116 IS 2 BP 525 EP 538 DI 10.1016/S0306-4522(02)00711-X PG 14 WC Neurosciences SC Neurosciences & Neurology GA 643MJ UT WOS:000180864800022 PM 12559108 ER PT J AU Serrano, J Encinas, JM Fernandez, AP Castro-Blanco, S Alonso, D Fernandez-Vizarra, P Richart, A Bentura, ML Santacana, M Cuttitta, F Martinez, A Rodrigo, J AF Serrano, J Encinas, JM Fernandez, AP Castro-Blanco, S Alonso, D Fernandez-Vizarra, P Richart, A Bentura, ML Santacana, M Cuttitta, F Martinez, A Rodrigo, J TI Distribution of immunoreactivity for the adrenomedullin binding protein, complement factor H, in the rat brain SO NEUROSCIENCE LA English DT Article DE immunohistochemistry; electron microscopy; confocal microscopy; immune surveillance ID CENTRAL-NERVOUS-SYSTEM; IN-VITRO; ALTERNATIVE PATHWAY; REGULATORY PROTEINS; GENE-EXPRESSION; C3B INACTIVATOR; CELL-LINES; HUMAN-SKIN; ADULT-RAT; PLASMA AB Adrenomedullin is a multifunctional amidated peptide that has been found in most nuclei of the CNS, where it plays a neuromodulatory role. An adrenomedullin binding protein has recently been found in plasma and characterized as complement factor H. This regulator of the complement system inhibits the progression of the complement cascade and modulates the function of adrenomedullin. Our study shows the ample distribution of factor H immunoreactivity in neurons of telencephalon, diencephalon, mesencephalon, pons, medulla, and cerebellum in the rat CNS, using immunohistochemical techniques for both light and electron microscopy. Factor H immunoreactivity was found in the cytoplasm, but nuclear staining was also a common finding. Some blood vessels and glial cells were also immunoreactive for factor H. Colocalization studies by double immunofluorescence followed by confocal microscopy revealed frequent coexistence of factor H and adrenomedullin immunoreactivities, thus providing morphological evidence for the potential interaction of these molecules in the CNS. The presence of factor H immunoreactivity in glial cells was confirmed by colocalization with glial fibrillary acidic protein. In summary, factor H is highly expressed in the CNS where it could play important roles in regulating adrenomedullin actions and contributing to an intracerebral complement system. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 CSIC, Inst Cajal, Dept Cell Biol & Neuroanat, E-28002 Madrid, Spain. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Rodrigo, J (reprint author), CSIC, Inst Cajal, Dept Cell Biol & Neuroanat, Ave Doctor Arce 37, E-28002 Madrid, Spain. RI Encinas, Juan/E-3625-2010; Fernandez-Vizarra, Paula/H-5588-2012; Martinez, Alfredo/A-3077-2013; OI Fernandez-Vizarra, Paula/0000-0002-0322-6844; Martinez, Alfredo/0000-0003-4882-4044; Encinas, Juan Manuel/0000-0002-0402-972X NR 54 TC 15 Z9 15 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2003 VL 116 IS 4 BP 947 EP 962 DI 10.1016/S0306-4522(02)00773-X PG 16 WC Neurosciences SC Neurosciences & Neurology GA 649XL UT WOS:000181233200004 PM 12617936 ER PT J AU Kesavapany, S Li, BS Pant, HC AF Kesavapany, S Li, BS Pant, HC TI Cyclin-dependent kinase 5 in neurofilament function and regulation SO NEUROSIGNALS LA English DT Review DE cyclin-dependent kinase 5 p35; neurofilaments; kinase; integrin; myelin-associated glycoprotein; signal transduction ID MYELIN-ASSOCIATED GLYCOPROTEIN; MOLECULAR-WEIGHT NEUROFILAMENT; AMYOTROPHIC-LATERAL-SCLEROSIS; NEURONAL INTERMEDIATE FILAMENTS; NERVE GROWTH-FACTOR; MONOCLONAL-ANTIBODIES DISTINGUISH; CERVICAL SPINAL-CORD; CDK5 ACTIVATOR P35; PROTEIN-KINASE; NF-H AB Neurofilaments are neuron-specific intermediate filaments. They are classed into three groups according to their molecular masses: neurofilament heavy, middle and light chains (NF-H, NF-M and NF-L). Neurofilaments assemble and form through the association of their central alpha-helical coiled-coil rod domains. NF-H and NF-M are distinct from NF-L as they contain a carboxyl-terminal tail domain, which appears to form connections with adjacent structures and other neurofilaments. Together with other axonal components such as microtubules, they form the dynamic axonal cytoskeleton. They maintain and regulate neuronal cytoskeletal plasticity through the regulation of neurite outgrowth, axonal caliber and axonal transport. Neurofilaments contain KSP repeats that are consensus motifs for the proline-directed kinases and are extensively phosphorylated in vivo, and their functions are thought to be regulated through their phosphorylation. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed kinase, whose activity is restricted to the neuron through the neuronal-specific distribution of its activators p35 and p39. Cdk5 is the only kinase that affects the electrophoretic mobility of human NF-H and is thought to be the major neurofilament kinase. Cdk5 is involved in crosstalk with other signal transduction pathways such as the mitogen-activated protein kinase and myelin-associated glycoprotein pathways to influence the phosphorylation of neurofilaments and other cytoskeletal proteins. Both the hyperactivation of Cdk5 activity and subsequent hyperphosphorylation of neurofilaments and the microtubule-associated protein tau have been implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis. Here we review the functions of neurofilaments and the significance of Cdk5 phosphorylation of neurofilaments. Copyright (C) 2003 S. Karger AG, Basel. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, 36 Convent Dr,MSC 4130, Bethesda, MD 20892 USA. NR 87 TC 42 Z9 44 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-862X J9 NEUROSIGNALS JI Neurosignals PY 2003 VL 12 IS 4-5 BP 252 EP 264 DI 10.1159/000074627 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences SC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences & Neurology GA 753BB UT WOS:000187210600012 PM 14673212 ER PT J AU Chase, TN Bibbiani, F Oh, JD AF Chase, TN Bibbiani, F Oh, JD TI Striatal glutamatergic mechanisms and extrapyramidal movement disorders SO NEUROTOXICITY RESEARCH LA English DT Review DE AMPA; Huntington disease; ionotropic receptor; LTP, medium spiny neuron; NMDA ID MOTOR RESPONSE ALTERATIONS; LEVODOPA-INDUCED DYSKINESIAS; NMDA RECEPTOR SUBUNITS; CENTRAL-NERVOUS-SYSTEM; MPTP-TREATED MONKEYS; KINASE-C PHOSPHORYLATION; L-DOPA TREATMENT; PARKINSONS-DISEASE; AMPA RECEPTOR; TYROSINE PHOSPHORYLATION AB The nonphysiologic stimulation of striatal dopaminergic receptors, as a result of disease- or drug-related denervation or intermittent excitation, triggers adaptive responses in the basal ganglia which contribute to the appearance of parkinsonian symptoms and later to the dyskinesias and other alterations in motor response associated with dopaminergic therapy. Current evidence suggests that these altered responses involve activation of signal transduction cascades in striatal medium spiny neurons linking dopaminergic to coexpressed ionotropic glutamatergic receptors of the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxa-zole proprionic acid (AMPA) classes. These intraneuronal signaling pathways appear capable of modifying the phosphorylation state of NMDA and AMPA receptor subunits; resultant sensitization enhances cortical glutamatergic input which in turn modifies striatal output in ways that compromise motor behavior. The regulation of these spiny neuron glutamate receptors can also be affected by the activation state of coexpressed nondopaminergic receptors as weft as by changes associated with Huntington's disease. These observations lend new insight into molecular mechanisms contributing to the integration of synaptic inputs to spiny neurons. They also suggest novel approaches to the pharmacotherapy of extrapyramidal motor dysfunction. C1 NINDS, NIH, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, NIH, Expt Therapeut Branch, Bldg 10,Room 5C103, Bethesda, MD 20892 USA. NR 105 TC 40 Z9 41 U1 0 U2 0 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2003 VL 5 IS 1-2 BP 139 EP 145 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 691MQ UT WOS:000183610400010 PM 12832228 ER PT J AU McPherson, CA Kubik, J Wine, RN D'Hellencourt, CL Harry, GJ AF McPherson, CA Kubik, J Wine, RN D'Hellencourt, CL Harry, GJ TI Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced hippocampal damage SO NEUROTOXICITY RESEARCH LA English DT Article; Proceedings Paper CT 1st Meeting of the Neurotoxicity-Society CY 2003 CL LA SERENA, CHILE SP Neurotoxic Soc DE cyclin; trimethyltin; glia; astrocytes; hippocampus; dentate gyrus ID COLONY-STIMULATING FACTOR; NEURONAL CELL-DEATH; SEIZURE-INDUCED NEUROGENESIS; ALZHEIMERS-DISEASE BRAIN; DEPENDENT KINASES; GROWTH-FACTOR; TRIMETHYLTIN INTOXICATION; STATUS EPILEPTICUS; CEREBRAL-ISCHEMIA; LIMBIC SEIZURES AB The interactions of glia and neurons during injury and subsequent neurodegeneration are a subject of interest both in disease and chemical-induced brain injury. One such model is the prototypical hippocampal toxicant trimethyltin (TMT). An acute injection of TMT (2.0 mg/kg, i.p.) to postnatal day 21 CD-1 male mice produced neuronal necrosis and loss of dentate granule cells, astrocyte hypertrophy, and microglia activation in the hippocampus within 24 h. Neuronal necrosis and microglia differentiation to a phagocytic phenotype is temporally correlated with peak elevations in TNF-alpha, cyclin A2, cyclin B1 and cyclin D1 at 72 h post-TMF. TNF-alpha mRNA levels were significantly elevated in the hippocampus by 12 h and remained elevated for 72 h. mRNA levels for cyclin A2 and cyclin B1 were elevated by approximately 2-fold at 72 h. Immunohistochemistry suggested a cellular localization of cyclin A to microglia in the region of neuronal necrosis in the dentate, cyclin B in glial cells in juxtaposition to neurons in the hilus of the hippocampus and cyclin D1 to non-glial cells in the dentate. mRNA levels for cyclin D1 were elevated approximately 1.5-fold by 72 h as determined by RNase protection assay. No changes were seen in mRNA levels for cyclins E, F, G1, G2, H or I nor cyclin dependent kinases. These elevations are not associated with proliferation of microglia as determined by BrdU incorporation and Ki-67 immunohistochemistry. Upregulation of cell cycle genes was associated with cellular processes other than proliferation and may contribute to the differentiation of microglia to a phagocytic phenotype. These data suggest an integrated role for cell cycle regulation of neural cells in the manifestation of hippocampal pathophysiology. C1 Natl Inst Environm Hlth Sci, Neurotoxicol Grp, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), Natl Inst Environm Hlth Sci, Neurotoxicol Grp, Res Triangle Pk, NC 27709 USA. EM Harry@niehs.nih.gov NR 69 TC 14 Z9 14 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2003 VL 5 IS 5 BP 339 EP + PG 15 WC Neurosciences SC Neurosciences & Neurology GA 741RA UT WOS:000186470000005 PM 14715453 ER PT J AU Rapoport, SI AF Rapoport, SI TI Coupled reductions in brain oxidative phosphorylation and synaptic function can be quantified and staged in the course of Alzheimer disease SO NEUROTOXICITY RESEARCH LA English DT Article; Proceedings Paper CT 1st Meeting of the Neurotoxicity-Society CY 2003 CL LA SERENA, CHILE SP Neurotoxic Soc DE Alzheimer disease; cytochrome oxidase; positron emission tomography; brain, energy; metabolism; oxidative phosphorylation; mitochondria; activation; glucose; blood flow; synapse; neurofibrillary tangles; senile plaques; mRNA ID AMYLOID PRECURSOR PROTEIN; CEREBRAL METABOLIC ASYMMETRIES; POSITRON EMISSION TOMOGRAPHY; LIGHT-STRAND TRANSCRIPTION; AGE-RELATED DIFFERENCES; SUBUNIT MESSENGER-RNA; OXIDASE COX ACTIVITY; CYTOCHROME-OXIDASE; MITOCHONDRIAL-DNA; NEURONAL-ACTIVITY AB In vivo, post-mortem and biopsy data suggest that coupled declines occur in brain synaptic activity and brain energy consumption during the evolution of Alzheimer disease. In the first stage of these declines, changes in synaptic structure and function reduce neuronal energy demand and lead to potentially reversible downregulation of oxidative phosphorylation (OXPHOS) within neuronal mitochondria. At this stage, measuring brain glucose metabolism or brain blood flow in patients, using positron emission tomography (PET), shows that the brain can be almost normally activated in response to stimulation. Thus, therapy at this stage should be designed to re-establish synaptic integrity or prevent its further deterioration. As disease progresses, neurofibrillary tangles with abnormally phosphorylated tau protein accumulate within neuronal cytoplasm, to the point that they co-opt the nonphosphorylated tau necessary for axonal transport of mitochondria between the cell nucleus and the synapse. In this second stage, severe energy depletion and other pathological processes associated with irreversibly downregulated OXPHOS lead to cell death, and the brain cannot normally respond to functional stimulation. C1 NIA, Brain Physiol Sect, NIH, Bethesda, MD 20892 USA. NIA, Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol Sect, NIH, Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. NR 95 TC 14 Z9 17 U1 2 U2 2 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2003 VL 5 IS 6 BP 385 EP 397 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 759HX UT WOS:000187733200002 PM 14715441 ER PT J AU Creveling, CR AF Creveling, CR TI Reduced COMT activity as a possible environmental risk factor for breast cancer. Opinion. SO NEUROTOXICITY RESEARCH LA English DT Article DE catechol-O-methyltransferase; breast cancer; catechol estrogens; isoflavenoids; polyphenols; vitamin D ID CATECHOL-O-METHYLTRANSFERASE; PREVENTION; CELLS AB Recent genetic epidemiological studies implicate a low activity form of catechol-O-methyltransferase (COMT) with increased risk factor for breast cancer. Taking into account, the role of COMT in the metabolism of otherwise carcinogenic catecholestrogens, it is reasonable to propose that environmental or dietary products that inhibit COMT pose a risk for breast cancer. C1 NIDDK, Chem Lab, NIH, Bethesda, MD 20814 USA. RP Creveling, CR (reprint author), NIDDK, Chem Lab, NIH, Bethesda, MD 20814 USA. EM CrevelingB@extra.niddk.nih.gov NR 15 TC 6 Z9 7 U1 0 U2 0 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2003 VL 5 IS 7 BP 473 EP 474 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 764YB UT WOS:000188233300001 PM 14715431 ER PT J AU Galligan, C Yoshimura, T AF Galligan, C Yoshimura, T TI Phenotypic and functional changes of cytokine-activated neutrophils SO NEUTROPHIL: AN EMERGING REGULATOR OF INFLAMMATORY AND IMMUNE RESPONSE SE CHEMICAL IMMUNOLOGY BS STUDIES IN EPISTEMOLOGY, LOGIC, METHODOLOGY, AND PHILOSOPHY OF SCIENCE LA English DT Review ID COLONY-STIMULATING FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; DELAYED-TYPE HYPERSENSITIVITY; TUMOR-NECROSIS-FACTOR; HUMAN POLYMORPHONUCLEAR NEUTROPHILS; SELECTIN GLYCOPROTEIN LIGAND-1; FRACTALKINE RECEPTOR CX(3)CR1; STEM-CELL MOBILIZATION; CC-CHEMOKINE RECEPTOR; HUMAN DENDRITIC CELLS C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Yoshimura, T (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 559,Rm 9, Frederick, MD 21702 USA. NR 123 TC 19 Z9 20 U1 0 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem.Immunol. PY 2003 VL 83 BP 24 EP 44 PG 21 WC Immunology SC Immunology GA BX25R UT WOS:000184743800002 PM 12947977 ER PT B AU Perry, TA Sambamurti, K Lahiri, DK Mattson, MP Egan, JM Greig, NH AF Perry, TA Sambamurti, K Lahiri, DK Mattson, MP Egan, JM Greig, NH BE Hanin, I Fisher, A Cacabelos, R TI The glucagon-like peptides: New therapeutic strategy for neurodegeneration SO NEW TRENDS IN ALZHEIMER AND PARKINSON RELATED DISORDERS LA English DT Proceedings Paper CT 6th International Conference on Progress in Alzheimers and Parkinsons Disease CY MAY 08-12, 2003 CL Seville, SPAIN ID EXENDIN-4; RECEPTOR; BRAIN; BETA AB Glucagon-like peptide - 1 (7-36) - amide (GLP-1) is an endogenous insulinotropic peptide, which lowers blood glucose levels and food intake in type-2 diabetic and non-diabetic patients. We have demonstrated that GLP-1 and its longer-acting analogue, exendin-4 have multiple synergistic effects on glucose-dependent insulin secretion pathways of the pancreatic beta-cell and on plasticity in neuronal cells. In line with their neurotrophic action (Perry et al., 2002a), we now show that these compounds are neuroprotective, can modify, APP processing and protect against oxidative injury, actions which suggest a novel therapeutic strategy for intervention in Alzheimer's disease (AD). C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,Natl Inst Hlth, Baltimore, MD USA. RP Perry, TA (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,Natl Inst Hlth, Baltimore, MD USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-7587-023-3 PY 2003 BP 75 EP 80 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BAC49 UT WOS:000221537200014 ER PT S AU Wulfkuhle, JD Paweletz, CP Steeg, PS Petricoin, EF Liotta, L AF Wulfkuhle, JD Paweletz, CP Steeg, PS Petricoin, EF Liotta, L BE LlombartBosch, A Felipo, V TI Proteomic approaches to the diagnosis, treatment, and monitoring of cancer SO NEW TRENDS IN CANCER FOR THE 21ST CENTURY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Cancer Symposium on New Trends in Cancer for the 21st Century CY NOV 10-13, 2002 CL VALENCIA, SPAIN ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; LASER CAPTURE MICRODISSECTION; PHOSPHORYLATED PROTEINS; FUNCTIONAL PROTEOMICS; MASS-SPECTROMETRY; MICROARRAYS; IDENTIFICATION; DISEASE; TARGETS; SERUM AB The field of proteomics holds promise for the discovery of new biomarkers for the early detection and diagnosis of disease, molecular targets for therapy and markers for therapeutic efficacy and toxicity. A variety of proteomics approaches may be used to address these goals. Two-dimensional gel electrophoresis (2D-PAGE) is the cornerstone of many discovery-based proteomics studies. Technologies such as laser capture microdissection (LCM) and highly sensitive MS methods are currently being used together to identify greater numbers of lower abundance proteins that are differentially expressed between defined cell populations. Newer technologies such as reverse phase protein arrays will enable the identification and profiling of target pathways in small biopsy specimens. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) analysis enables the high throughput characterization of lysates from very few tumor cells or body fluids and may be best suited for diagnosis and monitoring of disease. Such technologies are expected to supplement our arsenal of mRNA-based assays, and we believe that in the., future, entire cellular networks and not just a single deregulated protein will be the target of therapeutics and that we will soon be able to monitor the status of these pathways in diseased cells before, during and after therapy. C1 NCI, FDA, Clin Proteom Prog, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Womens Canc Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Clin Proteom Program, NCI, Bethesda, MD 20892 USA. RP Wulfkuhle, JD (reprint author), CBER, FDA, Bldg 29A-2B20,HFM 535,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 75 Z9 82 U1 1 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47762-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 532 BP 59 EP 68 PG 10 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BX19E UT WOS:000184568400007 PM 12908550 ER PT B AU Yao, JH Taylor, R AF Yao, JH Taylor, R GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Assessing accuracy factors in deformable 2D/3D medical image registration using a statistical pelvis model SO NINTH IEEE INTERNATIONAL CONFERENCE ON COMPUTER VISION, VOLS I AND II, PROCEEDINGS LA English DT Proceedings Paper CT 9th IEEE International Conference on Computer Vision CY OCT 13-16, 2003 CL NICE, FRANCE SP IEEE Comp Soc, TC Pattern Anal & Machine Intelligence DE deformable 2D-3D medical image registration; accuracy assessment; statistical model AB Deformable 2D-3D medical image registration is an essential technique in Computer Integrated Surgery (CIS) to fuse 3D pre-operative data with 2D intra-operative data. Several factors may affect the accuracy of 2D-3D registration, including the number of 2D views, the angle between views the view angle relative to anatomical objects, the co-registration error between views, the image noise, and the image distortion. In this paper, we investigate and assess the relationship between these factors and the accuracy of 2D-3D registration. We proposed a deformable 2D-3D registration method based on a statistical model. We conducted experiments using a hemi-pelvis model and simulated x-ray images. Some discussions are provided on how to improve the accuracy of 2D-3D registration based on our assessment. C1 NIH, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 2 Z9 2 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-1950-4 PY 2003 BP 1329 EP 1334 DI 10.1109/ICCV.2003.1238644 PG 6 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BX92L UT WOS:000186833000174 ER PT J AU Kelley, MW Lanford, PJ Jones, I Amma, L Ng, L Forrest, D AF Kelley, MW Lanford, PJ Jones, I Amma, L Ng, L Forrest, D TI Analysis of nuclear receptor function in the mouse auditory system SO NUCELAR RECEPTORS SE METHODS IN ENZYMOLOGY LA English DT Review ID THYROID-HORMONE RECEPTORS; RETINOIC ACID; HEARING-LOSS; HAIR-CELLS; INNER-EAR; MICE; CULTURE; CORTI; ORGAN; EXPRESSION C1 Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. RP Kelley, MW (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, 5 Res Court, Rockville, MD 20850 USA. FU NIDCD NIH HHS [DC-03441] NR 26 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 364 BP 426 EP 448 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX96L UT WOS:000187011900024 PM 14631859 ER PT J AU Kiesewetter, DO Jagoda, EM Kao, CHK Ma, Y Ravasi, L Shimoji, K Szajek, LP Eckelman, WC AF Kiesewetter, DO Jagoda, EM Kao, CHK Ma, Y Ravasi, L Shimoji, K Szajek, LP Eckelman, WC TI Fluoro-, bromo-, and iodopaclitaxel derivatives: synthesis and biological evaluation SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE pactitaxel; fluorine-18; bromine-76; iodine-124; P-glycoprotein; mdr1a/1b(-/-); rat; mice; tumor ID P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; TAXOL ANALOGS; DRUG-RESISTANCE; IN-VIVO; PACLITAXEL; EXPRESSION; REVERSAL; TISSUES; BRAIN AB Paclitaxel (Taxol(R)) is a clinically important chemotherapeutic agent. We describe the synthesis of fluoro-, bromo-, and iodopaclitaxel and their [F-18]fluoro-, [Br-76]bromo- and [I-124]iodo-analogues. [F-18]Fluoropaclitaxel shows high uptake and rapid clearance from tissues in rats. Preadministration of paclitaxel in normal rats significantly increases (p < 0.005) retention of [F-18]fluoropaclitaxel and [Br-76]bromopaclitaxel in blood (33.0%), heart (32.0%). lung (37.6%) kidney (142.4%) and blood (33.4%), lung (42.3%), kidney (62.4%), respectively. [F-18]Fluoropaclitaxel uptake in the brain of mdr1a/1b(-/-) mice is increased 1400% (p < 1.3e-07) relative to wild-type controls. Preadministration of paclitaxel or XR9576, a modulator. had little effect on the biodistribution in these mdr1a/1b(-/-) mice. As a result. [F-18]fluoropaclitaxel will be a useful radiopharmaceutical for the study of multidrug resistant tumors. Published by Elsevier Science Inc. All rights reserved. C1 NIH, Positron Emmiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIH, Positron Emmiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. NR 50 TC 45 Z9 45 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2003 VL 30 IS 1 BP 11 EP 24 AR PII S0969-8051(02)00351-7 DI 10.1016/S0969-8051(02)00351-7 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 631BN UT WOS:000180147200002 PM 12493538 ER PT J AU Kiesewetter, DO Vuong, BK Channing, MA AF Kiesewetter, DO Vuong, BK Channing, MA TI The automated radiosynthesis of [F-18]FP-TZTP SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE FP-TZTP; fluorine-18; muscarinic receptors AB [F-18]FP-TZTP (3-(3-(3-[F-18]fluoropropylthio)-1.2.5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine) is a muscarinic ligand that displays in vivo selectivity for the M2 subtype. We hake developed a one-step radiosynthesis of [F-18]FP-TZTP that can be conducted with an automated synthesis unit. A number of hardware and software modifications to a Nuclear Interface C-11 Methylation System provided the equipment for the automated radiosynthesis. The manual synthesis produced [F-18]FP-TZTP in a radiochemical yield of 23.4% +/- 4.3% (EOS, n = 69) with a specific activity of 4377 +/- 2011 mCi/mumol (EOB, n = 100). The automated synthesis unit provided the product in a radiochemical yield of 18.8% +/- 2.4% (EOS, n = 25) with a specific activity of 4112 +/- 2572 mCi/mumol (EOB, n = 25). Published by Elsevier Science Inc. All rights reserved. C1 NIH, Positron Emmiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIH, Positron Emmiss Tomog Dept, Ctr Clin, 10-1C401,10 Ctr Dr, Bethesda, MD 20892 USA. NR 5 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2003 VL 30 IS 1 BP 73 EP 77 AR PII S0969-8051(02)00354-2 DI 10.1016/S0969-8051(02)00354-2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 631BN UT WOS:000180147200009 PM 12493545 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI The Molecular Biology Database Collection: 2003 update SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The Molecular Biology Database Collection is an online resource listing key databases of value to the biological community. This Collection is intended to bring fellow scientists attention to high-quality databases that are available throughout the world, rather than just be a lengthy listing of all available databases. As such, this up-to-date listing is intended to serve as the jumping-off point from which to find specialized databases that may be of use in advancing biological research. The databases included in this Collection provide new value to the underlying data by virtue of curation, new data connections or other innovative approaches. Short, searchable summaries and updates for each of the databases included in this Collection are available through the Nucleic Acids Research Web site at http://nar.oupjournals.org. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bldg 50,Room 5222, Bethesda, MD 20892 USA. NR 2 TC 64 Z9 73 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 1 EP 12 DI 10.1093/nar/gkg120 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700001 PM 12519937 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Wheeler, DL AF Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Wheeler, DL TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSED SEQUENCE TAGS; DATABASE AB GenBank (R) is a comprehensive sequence database that contains publicly available DNA sequences for more than 119 000 different organisms, obtained primarily through the submission of sequence data from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the BankIt (web) or Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan helps ensure worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI home page at: http://www.ncbi.nlm.nih.gov. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 14 TC 258 Z9 279 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 23 EP 27 DI 10.1093/nar/gkg057 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700004 PM 12519940 ER PT J AU Wheeler, DL Church, DM Federhen, S Lash, AE Madden, TL Pontius, JU Schuler, GD Schriml, LM Sequeira, E Tatusova, TA Wagner, L AF Wheeler, DL Church, DM Federhen, S Lash, AE Madden, TL Pontius, JU Schuler, GD Schriml, LM Sequeira, E Tatusova, TA Wagner, L TI Database resources of the National Center for Biotechnology SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PSI-BLAST; PROTEIN; ENTREZ; TOOL; SEQUENCES AB In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, PubMed, PubMed Central (PMC), LocusLink, the NCBITaxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR (e-PCR), Open Reading Frame (ORF) Finder, References Sequence (RefSeq), UniGene, HomoloGene, ProtEST, Database of Single Nucleotide Polymorphisms (dbSNP), Human/Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes and related tools, the Map Viewer, Model Maker (MM), Evidence Viewer (EV), Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. OI Schriml, Lynn/0000-0001-8910-9851; Lash, Alex/0000-0003-3787-1590 NR 25 TC 514 Z9 537 U1 1 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 28 EP 33 DI 10.1093/nar/gkg033 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700005 PM 12519941 ER PT J AU Pruitt, KD Tatusova, T Maglott, DR AF Pruitt, KD Tatusova, T Maglott, DR TI NCBI Reference Sequence Project: update and current status SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESOURCES; DATABASE AB The goal of the NCBI Reference Sequence (RefSeq) project is to provide the single best non-redundant and comprehensive collection of naturally occurring biological molecules, representing the central dogma. Nucleotide and protein sequences are explicitly linked on a residue-by-residue basis in this collection. Ideally all molecule types will be available for each well-studied organism, but the initial database collection pragmatically includes only those molecules and organisms that are most readily identified. Thus different amounts of information are available for different organisms at any given time. Furthermore, for some organisms additional intermediate records are provided when the genome sequence is not yet finished. The collection is supplied by NCBI through three distinct pipelines in addition to collaborations with community groups. The collection is curated on an ongoing basis. Additional information about the NCBI RefSeq project is available at http://www.ncbi.nih.gov/RefSeq/. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,Room 6N605,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 8 TC 132 Z9 137 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 34 EP 37 DI 10.1093/nar/gkg111 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700006 PM 12519942 ER PT J AU Banerjee-Basu, S Moreland, T Hsu, BJ Trout, KL Baxevanis, AD AF Banerjee-Basu, S Moreland, T Hsu, BJ Trout, KL Baxevanis, AD TI The Homeodomain Resource: 2003 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING; CRYSTAL-STRUCTURE; COMPLEX AB The Homeodomain Resource is a searchable, curated collection of information for the homeodomain protein family. The resource is organized in a compact form and provides user-friendly interfaces for both querying the component databases and assembling customized datasets. The current release ( version 5.0, October 2002) contains 1056 full-length homeodomain-containing sequences, 37 experimentally-derived structures, 81 homeodomain interactions, 84 homeodomain DNA-binding sites and 114 homeodomain proteins implicated in human genetic disorders. A new feature of this new release is the inclusion of experimentally-derived protein protein interaction data for homeodomain family members. All entries are cross-linked for easy retrieval of the original records from source databases. The Homeodomain Resource is freely available through the World Wide Web at http://research.nhgri.nih.gov/homeodomain/. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 7 TC 19 Z9 19 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 304 EP 306 DI 10.1093/nar/gkg118 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700072 PM 12520008 ER PT J AU Marchler-Bauer, A Anderson, JB DeWeese-Scott, C Fedorova, ND Geer, LY He, SQ Hurwitz, DI Jackson, JD Jacobs, AR Lanczycki, CJ Liebert, CA Liu, CL Madej, T Marchler, GH Mazumder, R Nikolskaya, AN Panchenko, AR Rao, BS Shoemaker, BA Simonyan, V Song, JS Thiessen, PA Vasudevan, S Wang, YL Yamashita, RA Yin, JJ Bryant, SH AF Marchler-Bauer, A Anderson, JB DeWeese-Scott, C Fedorova, ND Geer, LY He, SQ Hurwitz, DI Jackson, JD Jacobs, AR Lanczycki, CJ Liebert, CA Liu, CL Madej, T Marchler, GH Mazumder, R Nikolskaya, AN Panchenko, AR Rao, BS Shoemaker, BA Simonyan, V Song, JS Thiessen, PA Vasudevan, S Wang, YL Yamashita, RA Yin, JJ Bryant, SH TI CDD: a curated Entrez database of conserved domain alignments SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The Conserved Domain Database (CDD) is now indexed as a separate database within the Entrez system and linked to other Entrez databases such as MEDLINE(R). This allows users to search for domain types by name, for example, or to view the domain architecture of any protein in Entrez s sequence database. CDD can be accessed on the WorldWide Web at http: / / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi? db = cdd. Users may also employ the CD-Search service to identify conserved domains in new sequences, at http: / / www. ncbi. nlm. nih. gov/ Structure/cdd/wrpsb.cgi. CD-Search results, and pre-computed links from Entrez s protein database, are calculated using the RPS-BLAST algorithm and Position Specific Score Matrices (PSSMs) derived from CDD alignments. CD-Searches are also run by default for protein protein queries submitted to BLAST 1 at http: / / www. ncbi. nlm. nih. gov/ BLAST. CDD mirrors the publicly available domain alignment collections SMART and PFAM, and now also contains alignment models curated at NCBI. Structure information is used to identify the core substructure likely to be present in all family members, and to produce sequence alignments consistent with structure conservation. This alignment model allows NCBI curators to annotate columns corresponding to functional sites conserved among family members. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; Abrams, Natalie/F-4845-2011; OI Abrams, Natalie/0000-0001-9698-2819; Marchler-Bauer, Aron/0000-0003-1516-0712 NR 10 TC 606 Z9 629 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 383 EP 387 DI 10.1093/nar/gkg087 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700092 PM 12520028 ER PT J AU Chen, J Anderson, JB DeWeese-Scott, C Fedorova, ND Geer, LY He, SQ Hurwitz, DI Jackson, JD Jacobs, AR Lanczycki, CJ Liebert, CA Liu, CL Madej, T Marchler-Bauer, A Marchler, GH Mazumder, R Nikolskaya, AN Rao, BS Panchenko, AR Shoemaker, BA Simonyan, V Song, JS Thiessen, PA Vasudevan, S Wang, YL Yamashita, RA Yin, JJ Bryant, SH AF Chen, J Anderson, JB DeWeese-Scott, C Fedorova, ND Geer, LY He, SQ Hurwitz, DI Jackson, JD Jacobs, AR Lanczycki, CJ Liebert, CA Liu, CL Madej, T Marchler-Bauer, A Marchler, GH Mazumder, R Nikolskaya, AN Rao, BS Panchenko, AR Shoemaker, BA Simonyan, V Song, JS Thiessen, PA Vasudevan, S Wang, YL Yamashita, RA Yin, JJ Bryant, SH TI MMDB: Entrez's 3D-structure database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLEX; KINASE AB dimensional structures are now known within most protein families and it is likely, when searching a sequence database, that one will identify a homolog of known structure. The goal of Entrez' s 3D- structure database is to make structure information and the functional annotation it can provide easily accessible to molecular biologists. To this end, Entrez' s search engine provides several powerful features: ( i) links between databases, for example between a protein s sequence and structure; ( ii) precomputed sequence and structure neighbors; and ( iii) structure and sequence/ structure alignment visualization. Here, we focus on a new feature of Entrez' s Molecular Modeling Database ( MMDB) : Graphical summaries of the biological annotation available for each 3D structure, based on the results of automated comparative analysis. MMDB is available at: http: / / www. ncbi. nlm. nih. gov/ Entrez/ structure. html. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; Abrams, Natalie/F-4845-2011; OI Abrams, Natalie/0000-0001-9698-2819; Marchler-Bauer, Aron/0000-0003-1516-0712 NR 12 TC 125 Z9 134 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2003 VL 31 IS 1 BP 474 EP 477 DI 10.1093/nar/gkg086 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647EP UT WOS:000181079700119 PM 12520055 ER PT J AU Chen, XC Matstuni, S Mitsuya, H Zemlicka, J AF Chen, XC Matstuni, S Mitsuya, H Zemlicka, J TI Synthesis of (Z)-(2,3-bis-hydroxymethyl)methylenecyclopropane analogues of purine nucleosides SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE nucleoside analogues; methylenecyclopropanes; anti-HIV agents; alkylation-elimination ID METHYLENECYCLOPROPANE ANALOGS; STEREOCHEMISTRY AB Synthesis of (Z)-(2,3-bis-hydroxymethyl)methylenecyclopropane analogues of nucleosides adenosine 10a, 10b, 10c and 17 is described. Epimerization of Feist's acid (11) using acetic anhydride gave cyclic anhydride 12 which was reduced in situ to give diol 13. Acetylation (compound 14) followed by addition of bromine led to dibromo derivative 15. Alkylation-elimination of adenine with 15 afforded, after deacetylation, analogue 10a. Similar treatment of 2-amino-6-chloropurine and 2,6-diaminopurine led to diacetates 16 and 18. Deprotection then gave compounds 17 and 10c. Hydrolysis of 17 furnished guanine analogue 10b. Compounds 10a, l0b or 10c were inactive against HCMV, HSV-1, HSV-2, EBV, VZV and HBV. Analogues 10a and 10b were also assayed for anti-HIV activity. Compound 10a was effective in HIV-1/MT-2 culture with EC50/CC50 33/> 100 muM but 10b was inactive. Analogue 10a was not a substrate for adenosine deaminase. C1 Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem,Dev Therapeut Program, Detroit, MI 48201 USA. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto, Japan. RP Zemlicka, J (reprint author), Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem,Dev Therapeut Program, Detroit, MI 48201 USA. EM zemlicka@kci.wayne.edu FU NIAID NIH HHS [P01-AI46390] NR 15 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 3 BP 265 EP 274 DI 10.1081/NCN-120021426 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 686DL UT WOS:000183305800003 PM 12816385 ER PT J AU Choi, Y Moon, HR Yoshimura, V Marquez, VE AF Choi, Y Moon, HR Yoshimura, V Marquez, VE TI Recent advances in the synthesis of confortnationally locked nucleosides and their success in probing the critical question of conformational preferences by their biological targets SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 15th International Roundtable Meeting on Nucleosides, Nucleotides and Nucleic Acids CY SEP 10-14, 2002 CL LEUVEN, BELGIUM SP Gilead Sci Inc, Ajinomoto Co, Berlin Chemie, Eurogentec, Biota, Berry & Associates, Glen Res, Novartis Pharmaceut, Trillink, Aventis Pharma, Merck, Idenix Pharmaceut, Pharmasset, Bruker, Honeywell, Indian Organ Chem Ltd, Link Technol, Oxford Univ Press, Bayer, CMS Chem Ltd, Triangle Pharmaceut, Tibotec, Amer Int Chem Inc, Roche Diagnost DE bicyclo[3.1.0]hexane and bicyclo[3.1.0]hexene; conformationally locked carbocyclic nucleosides; pseudorotational analysis; D4T and carbovir analogues; intramolecular cyclopropanation; lipase-catalyzed resolution ID CARBOCYCLIC NUCLEOSIDES; N-METHANOCARBATHYMIDINE; ANALOGS; CELLS AB The present work describes some recent approaches to the syntheses of three classes of locked-North nucleosides: beta-D-ribo-, beta-D-deoxyribo-, and beta-D-dideoxy-ribonucleosides. The method developed for the latter class permitted access to a novel bicyclo[3.1.0]hexene-type nucleosides structurally similar to D4T and carbovir. A structural analysis and biological activities are discussed. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH,HHS, Frederick, MD 21702 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH,HHS, 376 Boyles St, Frederick, MD 21702 USA. RI Choi, Yongseok/F-8375-2012 OI Choi, Yongseok/0000-0002-3622-3439 NR 17 TC 31 Z9 31 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 5-8 BP 547 EP 557 DI 10.1081/NCN-120021954 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 723NV UT WOS:000185439200005 PM 14565229 ER PT J AU Gmeiner, WH Yu, SY Pon, RT Pourquier, P Pommier, Y AF Gmeiner, WH Yu, SY Pon, RT Pourquier, P Pommier, Y TI Structural basis for topoisomerase I inhibition by nucleoside analogs SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 15th International Roundtable Meeting on Nucleosides, Nucleotides and Nucleic Acids CY SEP 10-14, 2002 CL LEUVEN, BELGIUM SP Gilead Sci Inc, Ajinomoto Co, Berlin Chemie, Eurogentec, Biota, Berry & Associates, Glen Res, Novartis Pharmaceut, Trillink, Aventis Pharma, Merck, Idenix Pharmaceut, Pharmasset, Bruker, Honeywell, Indian Organ Chem Ltd, Link Technol, Oxford Univ Press, Bayer, CMS Chem Ltd, Triangle Pharmaceut, Tibotec, Amer Int Chem Inc, Roche Diagnost DE topoisomerase 1; antimetabolite; DNA; cancer chemotherapy; Ara-C; gemcitabine ID MODEL OKAZAKI FRAGMENT; MEDIATED DNA-DAMAGE; NMR STRUCTURE; COMPLEXES; ANTIMETABOLITE; CYTARABINE; MECHANISM AB Nucleoside analogs such as I-P-D-arabinofuranosyl cytidine (AraC) and 2', 2'-difluoro deoxycytidine (dFdC) are important components of the anticancer chemotherapeutic arsenal and are among the most effective anticancer drugs currently available. Although both AraCTP and dFdCTP impede DNA replication through pausing of DNA polymerases, both nucleoside analogs are ultimately incorporated into replicated DNA and interfere in DNA-mediated processes. Our laboratories are investigating the structural basis for the poisoning of topoisomerase I (top1)due to antipyrimidine incorporation into duplex DNA. We recently reported that both AraC and dFdC induce formation of top1 cleavage complexes, and poisoning of top1 contributes to the anticancer activities of both these drugs. Recent NMR and thermodynamic studies from our laboratories provide insight into the mechanism by which AraC and dFdC poison top 1. NMR studies from our laboratories have revealed that the arabinosyl sugar of AraC adopted a C2'-endo conformation. Although this is a B-type sugar pucker characteristic of duplex DNA, the conformation is rigid, and this lack of flexibility probably contributes to inhibition of the religation step of the top 1 reaction. In contrast to AraC, NMR studies revealed dFdC adopted a C3' endo sugar pucker characteristic of RNA, rather than DNA duplexes. dFdC substitution enhanced formation of top1 cleavage complexes, but did not inhibit religation. The enhancement of top1 cleavage complexes most likely results from a combination of conformational and electrostatic effects. The structural effects of dFdC and AraC are being further investigated in duplex DNA with well-defined top1 cleavage sites to analyze more specifically how these structural perturbations lead to enzyme poisoning. C1 Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. Univ Calgary, Core DNA Synth Facil, Calgary, AB, Canada. Inst Bergonie, Lab Pharmacol Agens Anticanc, Bordeaux, France. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Gmeiner, WH (reprint author), Wake Forest Univ, Sch Med, Dept Biochem, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NCI NIH HHS [R01 CA060612] NR 15 TC 16 Z9 17 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 5-8 BP 653 EP 658 DI 10.1081/NCN-120022604 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 723NV UT WOS:000185439200022 PM 14565246 ER PT J AU Kim, HO Lim, MH Park, JG Moon, HR Jacobson, KA Kim, HD Chun, MW Jeong, LS AF Kim, HO Lim, MH Park, JG Moon, HR Jacobson, KA Kim, HD Chun, MW Jeong, LS TI Design and synthesis of A(3) adenosine receptor ligands, 3 '-fluoro analogues of Cl-IB-MECA SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 15th International Roundtable Meeting on Nucleosides, Nucleotides and Nucleic Acids CY SEP 10-14, 2002 CL LEUVEN, BELGIUM SP Gilead Sci Inc, Ajinomoto Co, Berlin Chemie, Eurogentec, Biota, Berry & Associates, Glen Res, Novartis Pharmaceut, Trillink, Aventis Pharma, Merck, Idenix Pharmaceut, Pharmasset, Bruker, Honeywell, Indian Organ Chem Ltd, Link Technol, Oxford Univ Press, Bayer, CMS Chem Ltd, Triangle Pharmaceut, Tibotec, Amer Int Chem Inc, Roche Diagnost DE A(3) adenosine receptor; 3 '-deoxy-3 '-fluoro-N-6-substituted adenosines ID RAT-BRAIN AB Synthesis of 3'-deoxy-3'-fluoro-N-6-substituted adenosines as bioisosteres of Cl-IB-MECA and their binding affinities to A(3) adenosine receptor are described. C1 Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. Seoul Natl Univ, Div Chem & Mol Engn, Seoul, South Korea. Seoul Natl Univ, Coll Pharm, Seoul, South Korea. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Sookmyung Womens Univ, Coll Pharm, Seoul, South Korea. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, 11-1 Seodaemun Gu, Seoul 120750, South Korea. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 6 TC 4 Z9 4 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 5-8 BP 923 EP 925 DI 10.1081/NCN-120022701 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 723NV UT WOS:000185439200088 PM 14565312 ER PT J AU Kim, HO Park, JG Moon, HR Gunaga, P Lim, MH Chun, MW Jacobson, KA Kim, HD Jeong, LS AF Kim, HO Park, JG Moon, HR Gunaga, P Lim, MH Chun, MW Jacobson, KA Kim, HD Jeong, LS TI Design and synthesis of A(3) adenosine receptor ligands, 2 '-fluoro analogues of Cl-IB-MECA SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 15th International Roundtable Meeting on Nucleosides, Nucleotides and Nucleic Acids CY SEP 10-14, 2002 CL LEUVEN, BELGIUM SP Gilead Sci Inc, Ajinomoto Co, Berlin Chemie, Eurogentec, Biota, Berry & Associates, Glen Res, Novartis Pharmaceut, Trillink, Aventis Pharma, Merck, Idenix Pharmaceut, Pharmasset, Bruker, Honeywell, Indian Organ Chem Ltd, Link Technol, Oxford Univ Press, Bayer, CMS Chem Ltd, Triangle Pharmaceut, Tibotec, Amer Int Chem Inc, Roche Diagnost DE A(3) adenosine receptor; 2 '-deoxy-2 '-fluoro-N-6-substituted ID RAT-BRAIN AB Synthesis of 2-deoxy-2'-fluoro-N-6-substituted adenosines as bioisosteres of Cl-IB-MECA and their binding affinities to A(3) adenosine receptor are described. C1 Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. Seoul Natl Univ, Div Chem & Mol Engn, Seoul, South Korea. Seoul Natl Univ, Coll Pharm, Seoul, South Korea. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Sookmyung Womens Univ, Coll Pharm, Seoul, South Korea. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, 11-1 Seodaemun Gu, Seoul 120750, South Korea. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 6 TC 4 Z9 4 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 5-8 BP 927 EP 930 DI 10.1081/NCN-120022687 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 723NV UT WOS:000185439200089 PM 14565313 ER PT J AU Ye, S Rezende, MM Deng, WP Kirk, KL AF Ye, S Rezende, MM Deng, WP Kirk, KL TI Convenient synthesis of 2 '-deoxy-2-fluoroadenosine from 2-fluoroadenine SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE fluorinated nucleosides; thioglycoside coupling; glycosylation; anomer separation ID NUCLEOSIDES AB A convenient synthesis of 2'-deoxy-2-fluoroadenosine from commercially available 2-fluoroadenine is described. The coupling reaction of silylated 2-fluoroadenine with phenyl 3,5-bis[O-(t-butyldimethylsilyl)]-2-deoxy-1-thio-D-erythro-pentofuranoside gave the corresponding 2-fluoro-2'-deoxyadenosine derivative (alpha/beta = 1:1) in good yield. The alpha- and beta-anomers were separated by chromatography, and then desilylated to give compounds 1a and 1b. C1 NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM kennethk@intra.niddk.nih.gov NR 6 TC 2 Z9 2 U1 2 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 10 BP 1899 EP 1905 DI 10.1081/NCN-120025237 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733CF UT WOS:000185981800003 PM 14609229 ER PT J AU Kundu, M Nagatsugi, F Majumdar, A Miller, PS Seidman, MM AF Kundu, M Nagatsugi, F Majumdar, A Miller, PS Seidman, MM TI Enhancement and inhibition by 2 '-O-hydroxyethyl residues of gene targeting mediated by triple helix forming oligonucleotides SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE triple helix; oligonucleotides; ribose analogue; bioactivity ID DOUBLE-STRANDED DNA; 3RD STRAND; 2'-AMINOETHOXY-MODIFIED OLIGONUCLEOTIDES; BACKBONE COMPOSITION; PHYSIOLOGICAL PH; DUAL RECOGNITION; CROSS-LINKING; RNA; SITES; SPECTROSCOPY AB Reagents that recognize and bind specific genomic sequences in living mammalian cells would have great potential for genetic manipulation, including gene knockout, strain construction, and gene therapy. Triple helix forming oligonucleotides (TFOs) bind specific sequences via the major groove, but pyrimidine motif TFOs are limited by their poor activity under physiological conditions. Base and sugar analogues that overcome many of these limitations have been described. In particular, 2'-O-modifications influence sugar pucker and third strand conformation, and have been important to the development of bioactive TFOs. Here we have analyzed the impact of 2'-O-hydroxyethyl (2'-HE) substitutions, in combination with other 2' modifications. We prepared modified TFOs conjugated to psoralen and measured targeting activity in a gene knockout assay in cultured hamster cells. We find that 2'-HE residues enhance the bioactivity of TFOs containing 2'-O-methyl (2'-OMe) modifications, but reduce the bioactivity of TFOs containing, in addition, 2'-O-aminoethyl (2'-AE) residues. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD USA. RP Seidman, MM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM seidmann@grc.nia.nih.gov NR 27 TC 3 Z9 3 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 10 BP 1927 EP 1938 DI 10.1081/NCN-120025240 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733CF UT WOS:000185981800006 PM 14609232 ER PT J AU Choi, YS Sun, GY George, C Nicklaus, MC Kelley, JA Marquez, VE AF Choi, YS Sun, GY George, C Nicklaus, MC Kelley, JA Marquez, VE TI Synthesis and conformational analysis of a locked analogue of carbovir built on a bicyclo[3.1.0]hex-2-enyl template SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE carbocyclic nucleosides; carbovir analogue; bicyclo[3.1.0]hex-2-enyl; template; conformationally locked; anti-HIV ID NUCLEOSIDES; 2',3'-DIDEHYDRO-2',3'-DIDEOXYGUANOSINE; PSEUDOROTATION; STAVUDINE; ABACAVIR; DENSITY; AGENT AB The synthesis and biological evaluation of a carbovir analogue (5) built on a bicyclo[3.1.0]hex-2-enyl template is described. A conformational analysis using density functional theory at the B3LYP/6-31G* level has been carried out on the rigid pseudosugar template of 5, the cyclopentene moiety of carbovir and the bicyclo[3.1.0]hex-2-yl pseudosugars of two isomeric carbonucleosides (12 and 13) containing exo- and endo-fused cyclopropane rings. The results show that while the planar configuration of the fused cyclopentane ring of compound 5 helps retain weak anti-HIV activity, the ability of the cyclopentene ring of carbovir to easily adopt a planar or puckered conformation with little energy penalty may prove to be a crucial advantage. The bicyclo[3.1.0]hex-2-yl nucleosides 12 and 13 that were inactive against HIV exhibited stiffer resistance to having a planar, fused cyclopentane moiety. C1 NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Med Chem LabNHI, Frederick, MD 21702 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Med Chem LabNHI, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov RI Nicklaus, Marc/N-4183-2014; Choi, Yongseok/F-8375-2012 OI Choi, Yongseok/0000-0002-3622-3439 NR 23 TC 8 Z9 8 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1525-7770 EI 1532-2335 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2003 VL 22 IS 12 BP 2077 EP 2091 DI 10.1081/NCN-120026631 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753DF UT WOS:000187216100002 PM 14714758 ER PT J AU Grady, PA AF Grady, PA TI A NINR initiatiive to address health disparities SO NURSING OUTLOOK LA English DT Editorial Material C1 NINR, NIH, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 2003 VL 51 IS 1 BP 5 EP 5 DI 10.1067/mno.2003.010011 PG 1 WC Nursing SC Nursing GA 648NH UT WOS:000181157100003 PM 12595820 ER PT J AU Lomnitski, L Bergman, M Nyska, A Ben-Shaul, V Grossman, S AF Lomnitski, L Bergman, M Nyska, A Ben-Shaul, V Grossman, S TI Composition, efficacy, and safety of spinach extracts SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID WATER-SOLUBLE ANTIOXIDANT; NEURONAL SIGNAL-TRANSDUCTION; NATURAL ANTIOXIDANTS; OXIDATIVE STRESS; VITAMIN-A; FLAVONOL GLYCOSIDES; BEHAVIORAL DEFICITS; CATARACT-EXTRACTION; INDUCED ENDOTOXEMIA; BREAST-CANCER AB Spinach leaves, containing several active components, including flavonoids, exhibit antioxidative, antiproliferative, and and inflammatory properties in biological systems. Spinach extracts have been demonstrated to exert numerous beneficial effects, such as chemo- and central nervous system protection and anticancer and antiaging functions. In this review article, we present a compilation of data generated in our laboratories and those of other investigators describing the chemical composition of spinach, its beneficial effects, relative safety information, and its recommended inclusion in the human diet. A powerful, water-soluble, natural antioxidant mixture (NAO), which specifically inhibits the lipoxygenase enzyme, was isolated from spinach leaves. The antioxidative activity of NAO has been compared to that of other known antioxidants and found to be superior in vitro and in vivo to that of green tea, N-acetylcysteine (NAC), butylated hydroxytoluene (BHT), and vitamin E. NAO has been tested for safety and is well tolerated in several species, such as mouse, rat, and rabbit. NAO has been found to be nonmutagenic and has shown promising anticarcinogenic effects in a few experimental models, such as skin and prostate cancer; it has not shown any target-organ toxicity or side effects. The current review provides epidemiological and preclinical data supporting the efficacy of extracts of spinach and the safety of its consumption. C1 Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Grossman, S (reprint author), Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. EM grossms@mail.biu.ac.il NR 71 TC 27 Z9 28 U1 1 U2 10 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2003 VL 46 IS 2 BP 222 EP 231 DI 10.1207/S15327914NC4602_16 PG 10 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 750FN UT WOS:000186980800016 PM 14690799 ER PT J AU Fu, YM Yu, ZX Li, YQ Ge, XK Sanchez, PJ Fu, X Meadows, GG AF Fu, YM Yu, ZX Li, YQ Ge, XK Sanchez, PJ Fu, X Meadows, GG TI Specific amino acid dependency regulates invasiveness and viability of androgen-independent prostate cancer cells SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FOCAL ADHESION KINASE; ACTIVATED PROTEIN-KINASE; INTEGRIN-MEDIATED ACTIVATION; MELANOMA IN-VITRO; PHENYLALANINE RESTRICTION; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; METASTATIC PHENOTYPE; GROWTH-FACTOR AB Androgen-independent prostate cancer is resistant to therapy and is often metastatic. Here we studied the effect of deprivation of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), in vitro on human DU145 and PC3 androgen-independent prostate cancer cells, and on nontumorigenic human infant foreskin fibroblasts and human prostate epithelial cells. Deprivation of the amino acids similarly inhibited growth of DU145 and PC3 cells, arresting the cell cycle at G0/G1 Met and Tyr/Phe deprivation induces apoptosis in DU145, but only Met deprivation induces apoptosis in PC3 cells. The growth of normal cells is inhibited, but no apoptosis is induced by amino acid deprivation. Tyr/Phe deprivation inhibits expression and phosphorylation of focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) in DU145 but not PC3 or normal cells. Met deprivation inhibits phosphorylation but not protein expression of FAK and ERK in PC3. Therefore, apoptosis of DU145 and PC3 cells by amino acid restriction is FAK and ERK dependent. Tyr/Phe and Met deprivation inhibits invasion of DU145 and PC3, but Gln deprivation only inhibits invasion of DU145 cells. This indicates that the inhibition of invasion is not dependent on induction of apoptosis. The inhibition of invasion by Tyr/Phe restriction in DU145 and Met restriction in PC3 is consistent with the inhibition on FAK/ERK signaling. The inhibition of Tyr/Phe restriction in PC3 and Gln restriction in DU145 is not associated with inhibition of FAK/ERK. This indicates that FAK/ERK-dependent and independent pathways are modulated by specific amino acid restriction. This study shows the potential for specific amino acid restriction to treat prostate cancer. C1 Washington State Univ, Coll Pharm, Dept Pharmaceut Sci,Canc Prevent & Res Ctr, Pharmacol & Toxicol Grad Program, Pullman, WA 99164 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. RP Meadows, GG (reprint author), Washington State Univ, Coll Pharm, Dept Pharmaceut Sci,Canc Prevent & Res Ctr, Pharmacol & Toxicol Grad Program, Box 646510, Pullman, WA 99164 USA. FU NCI NIH HHS [R01CA77604] NR 69 TC 25 Z9 40 U1 1 U2 5 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2003 VL 45 IS 1 BP 60 EP 73 DI 10.1207/S15327914NC4501_8 PG 14 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 691CL UT WOS:000183587200008 PM 12791506 ER PT J AU Russell, RB Petrini, JR Damus, K Mattison, DR Schwarz, RH AF Russell, RB Petrini, JR Damus, K Mattison, DR Schwarz, RH TI The changing epidemiology of multiple births in the United States SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB OBJECTIVE: To describe changes in the epidemiology of multiple births in the United States from 1980 to 1999 by race, maternal age, and region; and to examine the impact of these changes on birth weight-specific infant mortality rates for singleton and multiple births. METHODS: Retrospective univariate and multivariable analyses were conducted using vital statistics data from the National Center for Health Statistics. RESULTS: Between 1980 and 1999, the overall multiple birth ratio increased 59% (from 19.3 to 30.7 multiple births per 1000 live births, P < .001), with rates among whites increasing more rapidly than among blacks. Women of advanced maternal age, especially those aged 30-34, 3539, and 40-44 experienced the greatest increases (62%, 81%, and 110%, respectively). Although all regions of the United States experienced increases in multiple birth ratios between 1991 and 1999, the Northeast had the highest twin (33.9 per 1000 live births) and higher order birth ratios (280.5 per 100,000 live births), even after adjusting for maternal age and race. Between 1989 and 1999, multiple births experienced greater declines in infant mortality than singletons in all birth weight categories. Consequently, very low birth weight and moderately low birth weight infant mortality rates among multiples were lower than among singletons. CONCLUSION: It is important to understand the changing epidemiology of multiple births, especially for women at highest risk (advanced maternal age, white race, Northeast residents). The attribution of infertility management requires further study. The differential birth weight-specific infant mortality for singletons and multiples demonstrates the importance of stratifying by plurality when assessing perinatal outcomes. (C) 2003 by The American College of Obstetricians and Gynecologists. C1 March Dimes Birth Defects Fdn, Perinatal Data Ctr, White Plains, NY 10605 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Cornell Univ, New York Methodist Hosp, New York, NY USA. Cornell Univ, Weill Med Coll, New York, NY USA. RP Russell, RB (reprint author), 1275 Mamaroneck Ave, White Plains, NY 10605 USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 21 TC 127 Z9 129 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2003 VL 101 IS 1 BP 129 EP 135 AR PII S0029-7844(02)02316-5 DI 10.1016/S0029-7844(02)02316-5 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 632UN UT WOS:000180241800023 PM 12517657 ER PT J AU Neimeyer, RA Moser, RP Wittkowski, J AF Neimeyer, RA Moser, RP Wittkowski, J TI Assessing attitudes toward dying and death: Psychometric considerations SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Review ID COLLETT-LESTER FEAR; PERSONAL DEATH; HASTENED DEATH; ANXIETY SCALE; MEASURING-DESIRE; CANCER-PATIENTS; ILL PATIENTS; DEPRESSION; LIFE; VALIDATION AB In the 50 years of research in death attitudes, clear gains have been made in the measurement of death concerns and competencies, leading to the development and validation of several scales whose more extensive use could improve the conceptual yield of research in this area. In this article, we review these promising instruments, focusing on nine general questionnaires for measuring death anxiety, fear, threat, depression, and acceptance, and four specialized measures of death self-efficacy and coping, readiness for death, and desire for hastened death. We also offer an orientation to non-questionnaire based techniques for the assessment of death attitudes (e.g., narrative measures, repertory grids, behavioral observations, death personifications and drawings), and close with a note on international developments that hold promise for improved cultural awareness of the role of death attitudes in human life. C1 Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. NCI, Bethesda, MD 20892 USA. Univ Wurzburg, D-97070 Wurzburg, Germany. RP Neimeyer, RA (reprint author), Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. EM neimeyer@memphis.edu NR 120 TC 54 Z9 54 U1 1 U2 16 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2003 VL 47 IS 1 BP 45 EP 76 PG 32 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 764XZ UT WOS:000188233100003 ER PT J AU Berger, A AF Berger, A TI Treating fatigue in cancer patients SO ONCOLOGIST LA English DT Article; Proceedings Paper CT All Ireland Fatigue Coalition Meeting CY SEP 13-14, 2002 CL DUBLIN, IRELAND DE fatigue; neoplasms; depression; anemia; sleep disorders ID BONE-MARROW TRANSPLANTATION; QUALITY-OF-LIFE; CHEMOTHERAPY; OUTCOMES; THERAPY AB Possible causes of cancer-related fatigue include depression, pain, sleep problems, anemia, deconditioning, metabolic abnormalities, infection, dietary problems, hypoxia, and side effects of medication. Although treatments are available for each of these conditions, there are no generally accepted treatments available for the whole fatigue syndrome. There are also very few studies on the treatment of cancer-related fatigue-only 10 randomized controlled trials. Health care providers have begun to understand that, just as the treatment of pain requires attention to imbalances in mind, body, and spirit, the treatment of fatigue will require such an approach. C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Berger, A (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 2N236, Bethesda, MD 20892 USA. NR 12 TC 34 Z9 34 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 SU 1 BP 10 EP 14 DI 10.1634/theoncologist.8-suppl_1-10 PG 5 WC Oncology SC Oncology GA 657MU UT WOS:000181671600004 PM 12626782 ER PT J AU Curt, G Johnston, PG AF Curt, G Johnston, PG TI Cancer fatigue: The way forward SO ONCOLOGIST LA English DT Article; Proceedings Paper CT All Ireland Fatigue Coalition Meeting CY SEP 13-14, 2002 CL DUBLIN, IRELAND AB Research in cancer-related fatigue lags far behind research in cancer-related pain and is astonishingly underdeveloped given the magnitude of the problem among cancer patients. This was recently recognized at the State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue, held at the U.S. National Institutes of Health in July 2002. The results of patient surveys on fatigue being conducted in Ireland by the All Ireland Fatigue Coalition (AIFC) closely mirror results from similar surveys conducted in the U.S., in some regards, with 53% of patients experiencing significant fatigue at least daily, and 80% at least monthly on both sides of the Atlantic. In other respects, such as duration of bouts of fatigue, how much and with whom patients discuss their fatigue symptoms, and economic impacts of fatigue, there are significant differences between survey findings in the U.S. and in Ireland. But in both places, the condition is underreported and undertreated and takes an enormous toll. Work by the AIFC to document the problem in Ireland, expand public awareness, and conduct research on which to base guidelines for diagnosis and treatment is an excellent beginning to tackling this long understudied condition that afflicts the overwhelming majority of cancer patients. C1 Belfast City Hosp, Belfast BT9 7AD, Antrim, North Ireland. Queens Univ Belfast, All Ireland Fatigue Coalit, Belfast, Antrim, North Ireland. NCI, Bethesda, MD 20892 USA. RP Curt, G (reprint author), 1 Prestige Pl, Miamisburg, OH 45342 USA. NR 4 TC 29 Z9 29 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 SU 1 BP 27 EP 30 PG 4 WC Oncology SC Oncology GA 657MU UT WOS:000181671600008 PM 12626786 ER PT J AU Leonard, GD Fojo, T Bates, SE AF Leonard, GD Fojo, T Bates, SE TI The role of ABC transporters in clinical practice SO ONCOLOGIST LA English DT Review DE cancer; ABC transporter; multidrug resistance; chemotherapy; clinical trial ID ACUTE MYELOID-LEUKEMIA; RESISTANCE-ASSOCIATED PROTEIN; CELL LUNG-CANCER; P-GLYCOPROTEIN EXPRESSION; SOUTHWEST-ONCOLOGY-GROUP; ADVANCED BREAST-CANCER; WEEKLY ORAL PACLITAXEL; BINDING CASSETTE ABC; IN-VITRO RESISTANCE; MULTIDRUG-RESISTANCE AB Drug resistance remains one of the primary causes of suboptimal outcomes in cancer therapy. ATP-binding cassette (ABC) transporters are a family of transporter proteins that contribute to drug resistance via ATP-dependent drug efflux pumps. P-glycoprotein (P-gp), encoded by the MDR1 gene, is an ABC transporter normally involved in the excretion of toxins from cells. It also confers resistance to certain chemotherapeutic agents. P-gp is overexpressed at baseline in chemotherapy-resistant tumors, such as colon and kidney cancers, and is upregulated after disease progression following chemotherapy in malignancies such as leukemia and breast cancer. Other transporter proteins mediating drug resistance include those in the multidrug-resistance-associated protein (MRP) family, notably MRP1, and ABCG2. These transporters are also involved in normal physiologic functions. The expressions of MRP family members and ABCG2 have not been well worked out in cancer. Increased drug accumulation and drug resistance reversal with P-gp inhibitors have been well documented in vitro, but only suggested in clinical trials. Limitations in the design of early resistance reversal trials contributed to disappointing results. Despite this, three randomized trials have shown statistically significant benefits with the use of a P-gp inhibitor in combination with chemotherapy. Improved diagnostic techniques aimed at the selection of patients with tumors that express P-gp should result in more successful outcomes. Further optimism is warranted with the advent of potent, nontoxic inhibitors and new treatment strategies, including the combination of new targeted therapies with therapies aimed at the prevention of drug resistance. C1 NCI, Canc Therapeut Branch, Canc Res Ctr, Mol Therapeut Sect, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Canc Therapeut Branch, Canc Res Ctr, Mol Therapeut Sect, Bldg 10 Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 115 TC 440 Z9 475 U1 2 U2 37 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 5 BP 411 EP 424 DI 10.1634/theoncologist.8-5-411 PG 14 WC Oncology SC Oncology GA 729YR UT WOS:000185802900002 PM 14530494 ER PT J AU Ries, LAG Reichman, ME Lewis, DR Hankey, BF Edwards, BK AF Ries, LAG Reichman, ME Lewis, DR Hankey, BF Edwards, BK TI Cancer survival and incidence from the surveillance, epidemiology, and end results (SEER) program SO ONCOLOGIST LA English DT Article DE SEER; cancer; survival; incidence; mortality; prevalence ID BREAST-CANCER; TRENDS; RATES; AGE AB An overview of data on cancer at all sites combined and on selected, frequently occurring cancers is presented. Descriptive cancer statistics include average annual Surveillance, Epidemiology, and End Results (SEER) Program incidence, US. mortality and median age at diagnosis, and death for the period 1996-2000. Changes during the time period 1992-2000 are summarized by the annual percent change in SEER incidence and U.S. mortality data for this period. Five-year relative survival for selected cancers is examined by stage at diagnosis, based on data from 1990-1999. In addition, 5-year conditional survival for patients already surviving for 1-3 years after diagnosis is discussed as well as relative survival for other time periods. These measures may be more meaningful for clinical management and prognosis than 5-year relative survival from time of diagnosis. The likelihood of developing cancer during one's lifetime is 1 in 2 for males and I in 3 for females, based on 1998-2000 data. It is estimated that approximately 9.6 million people in the U.S. who have had a diagnosis of cancer are alive. Five-year relative survival varies greatly by cancer site and stage at diagnosis, and tends to increase with time since diagnosis. The median age at cancer diagnosis is 68 for men and 65 for women. The 5-year relative survival rate for persons diagnosed with cancer is 62.7%, with variation by cancer site and stage at diagnosis. For patients diagnosed with cancers of the prostate, female breast, corpus uteri, and urinary bladder, the relative survival rate at 8 years is over 75%. C1 NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Reichman, ME (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA. NR 22 TC 175 Z9 179 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 6 BP 541 EP 552 PG 12 WC Oncology SC Oncology GA 748LG UT WOS:000186862900009 PM 14657533 ER PT J AU Fujishita, T Loda, M Turner, RE Gentler, M Kashii, T Breathnach, OS Johnson, BE AF Fujishita, T Loda, M Turner, RE Gentler, M Kashii, T Breathnach, OS Johnson, BE TI Sensitivity of non-small-cell lung cancer cell lines established from patients treated with prolonged infusions of paclitaxel SO ONCOLOGY LA English DT Article DE carcinoma; non-small-cell lung neoplasm; docetaxel; paclitaxel; multidrug resistance; HER2/neu ID PHASE-II TRIAL; 96-HOUR CONTINUOUS-INFUSION; HER-2/NEU GENE-EXPRESSION; PROSTATE-CANCER; OVARIAN-CANCER; PROTEIN MRP; CISPLATIN; CYTOTOXICITY; TAXOTERE; TAXOL AB Objective: Regimens with prolonged infusions of taxanes have been developed for patients with cancer to overcome drug resistance. Our objective of the present study was to examine the impact of prolonged exposure on the cytotoxicity of taxanes against non-small-cell lung carcinoma (NSCLC) cell lines and the clinical response and outcome of the patients. Methods: Five cell lines (NCl-H2882, -H2887, -H2973, -H3122, -H3255) were derived from previously untreated patients with NSCLC who participated in clinical trials of continuous 96-hour infusions of paclitaxel followed by bolus cisplatin. Two additional cell lines (NCl-H838, -H1299) with previously published data were used as controls. Drug sensitivities were assessed by the MTS (Promega) assay. Multidrug resistance (MDR) phenotypes were assessed by quantitative real-time PCR and HER-2/neu by both immunohistochemistry and ELISA. Results: The median of mean IC50 values of docetaxel at the exposure durations of 3, 24, 72 and 120 h were 0.52, 0.06, 0.03 and 0.06 muM, respectively. The median of mean IC50 values of paclitaxel at the exposure duration of 3, 24, 72 and 120 h were 0.48, 0.13, 0.03 and 0.02 muM, respectively. In all cell lines studied, there was a less than 4-fold difference in the IC50 values between docetaxel and paclitaxel at 3-, 72-, and 120-hour exposure times. The single cell line with moderate MDR1 expression (NCl-H2887) was the only cell line established from a patient with progressive disease when treated with paclitaxel. Conclusions: This study demonstrates prolonged exposure to both docetaxel and paclitaxel inhibits the growth of NSCLC cell lines in similar fashion. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Natl Canc Inst, Bethesda, MD USA. Toyama Med & Pharmaceut Univ, Dept Internal Med 1, Toyama, Japan. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Dana 1234,44 Binney St, Boston, MA 02115 USA. NR 30 TC 13 Z9 15 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2003 VL 64 IS 4 BP 399 EP 406 DI 10.1159/000070299 PG 8 WC Oncology SC Oncology GA 681TA UT WOS:000183050400016 PM 12759538 ER PT J AU Chen, Y Petersen, S Pacyna-Gengelbach, M Pietas, A Petersen, I AF Chen, Y Petersen, S Pacyna-Gengelbach, M Pietas, A Petersen, I TI Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer SO ONCOLOGY LA English DT Article DE lung tumor cell line; lung primary tumors; suppression subtractive hybridization; homeobox gene; mRNA expression; gene mapping ID COMPARATIVE GENOMIC HYBRIDIZATION; MESSENGER-RNA EXPRESSION; CELL; CARCINOMAS; TUMORS; ADENOCARCINOMA; CLASSIFICATION; METASTASES; REGIONS; HOX AB We have isolated a novel gene, lung cancer-associated gene Y (LAGY), by suppression subtractive hybridization. The nucleotide sequence of LAGY predicts a small protein of 73 amino acids containing a putative homeobox domain with a molecular mass of 8.1 kD. Multipletissue Northern blot analysis revealed that LAGY is present in human placenta, lung, brain, heart and skeletal muscle. Gene mapping locates LAGY on chromosome 4q11-13.1. The expression of LAGY mRNA was widely lost in 18 lung tumor cell lines comprising all major histological types, as shown by Northern blot analysis and semiquantitative reverse transcriptionpolymerase chain reaction. In an investigation of 72 primary lung tumors, this gene was significantly downregulated in tumors compared to 9 normal lung tissue samples. There was a significant reduction of LAGY expression in squamous cell carcinoma (SCC; n = 27) with increasing grade and stage. No expression was detectable in two high-grade SCCs or two small cell and large cell lung carcinomas (n = 4 for each). In adenocarcinoma (n = 37), expression was reduced; however, this did not reach statistical significance. Since homeodomain-containing genes are known to transcriptionally regulate key cellular processes and are associated with carcinogenesis, we suggest that LAGY might be linked to lung cancer development and progression. C1 Humboldt Univ, Charite Med Sch, Inst Pathol, D-10098 Berlin, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Petersen, I (reprint author), Humboldt Univ, Charite Med Sch, Inst Pathol, D-10098 Berlin, Germany. NR 30 TC 29 Z9 32 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2003 VL 64 IS 4 BP 450 EP 458 DI 10.1159/000070306 PG 9 WC Oncology SC Oncology GA 681TA UT WOS:000183050400023 PM 12759545 ER PT J AU Pavletic, SZ AF Pavletic, SZ TI Nonmyeloablative preparative regimens for allogeneic hematopoietic transplantation - Biology and current indications - The Champlin/Khouri/Anderlini et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BONE-MARROW C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2003 VL 17 IS 1 BP 103 EP 104 PG 2 WC Oncology SC Oncology GA 639EP UT WOS:000180614900014 ER PT J AU Tsujishita, Y AF Tsujishita, Y TI Structural Genomics of lipid signaling domains SO ONCOLOGY RESEARCH LA English DT Article; Proceedings Paper CT Millennium International Conference on Molecular and Yumor Biology (MICMTB) CY SEP, 2001 CL SANTORINI, GREECE DE signaling domains; structural genomics; START domain; IPP5C domain ID ACUTE REGULATORY PROTEIN; INOSITOL POLYPHOSPHATE 5-PHOSPHATASES; PHOSPHATIDYLCHOLINE TRANSFER PROTEIN; LIPOID ADRENAL-HYPERPLASIA; CRYSTAL-STRUCTURE; MOLTEN-GLOBULE; SACCHAROMYCES-CEREVISIAE; LOWE-SYNDROME; CELL-LINES; X-RAY AB Signaling domains have been identified by the analysis of data derived from biochemical studies, molecular cloning, or genetic studies. With the availability of genomic information from many organisms and the improved sensitivity in homology detection techniques, many new domains are being identified. In an attempt to understand biochemical and biological function of these domains, we have started a small-scale structural genomics, or structural biology with genomic approach. Two examples from our recent work are steroidogenic acute regulatory protein (StAR)-related lipid-transfer (START) domain and inositol polyphosphate 5-phosphatase catalytic (IPP5C) domain. Crystal structure of human MLN64-START domain revealed a hollowed-out protein containing a hydrophobic tunnel just large enough to bind one molecule of cholesterol and completely exclude it from solvent. This structure suggests that the START domain is a classical type of lipid transporter. On the contrary, the function of IPP5C domain has been extensively studied for a long time, but its catalytic mechanism, positional selectivity, and diverse substrate specificity remained mysterious due to the unavailability of three-dimensional structure. With the structural genomic approach, the first structure of IPP5C domain was solved from a S. pombe protein that is now known as SPsynaptojanin and the structure gave us answers to some of these questions. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tsujishita, Y (reprint author), Univ Calif Berkeley, Dept Chem, Melvin Calvin Lab 250, Berkeley, CA 94720 USA. NR 70 TC 1 Z9 1 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 2003 VL 13 IS 6-10 BP 421 EP 428 PG 8 WC Oncology SC Oncology GA 669NW UT WOS:000182358200018 PM 12725533 ER PT J AU Holland, EJ Djalilian, AR Schwartz, GS AF Holland, EJ Djalilian, AR Schwartz, GS TI Management of aniridic keratopathy with keratolimbal allograft: A limbal stem cell transplantation technique SO OPHTHALMOLOGY LA English DT Article ID OCULAR-SURFACE DISEASE; AUTOSOMAL-DOMINANT ANIRIDIA; PENETRATING KERATOPLASTY; RECONSTRUCTION; DISORDERS AB Objective: Aniridic keratopathy is a major cause of vision loss in patients with aniridia. Penetrating keratoplasty has been proven ineffective for the long-term treatment of this disorder because it does not address the stem cell deficiency that is the primary etiologic factor. We evaluated the role of keratolimbal allograft (KLAL), a stem cell transplantation technique, for the treatment of patients with aniridic keratopathy. Design: Retrospective noncomparative interventional case series. Participants: Thirty-one eyes of 23 patients with aniridic keratopathy. Intervention: KLAL. Main Outcome Measures: Ocular surface stability, visual acuity, and success of subsequent penetrating or lamellar keratoplasty. Results: Thirty-one eyes of 23 patients were treated with KLAL and followed up for 12 toll 7 months (mean, 35.7 months). Twenty-three eyes (74.2%) achieved a stable ocular surface. Overall, the mean visual acuity improved from 20/1000 to 20/165. Twenty eyes (64.5%) underwent subsequent penetrating keratoplasty. Fourteen corneal transplant grafts (70.0%) were successful, and six (30.0%) failed. Nineteen (90.5%) of 21 eyes receiving systemic immunosuppression obtained a stable ocular surface, whereas only 4 (40.0%) of 10 eyes not receiving systemic immunosuppression achieved ocular surface stability (P < 0.01). Conclusions: KLAL is effective in treating aniridic keratopathy. Patients receiving systemic immunosuppression have a greater likelihood of achieving ocular surface stability and improved visual acuity compared with those who receive only topical immunosuppression. (C) 2003 by the American Academy of Ophthalmology. C1 Univ Cincinnati, Cincinnati Eye Inst, Cincinnati, OH 45242 USA. NEI, NIH, Washington, DC USA. Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. RP Holland, EJ (reprint author), Univ Cincinnati, Cincinnati Eye Inst, Cincinnati, OH 45242 USA. NR 23 TC 85 Z9 93 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2003 VL 110 IS 1 BP 125 EP 130 AR PII S0161-6420(02)01451-3 DI 10.1016/S0161-6420(02)01451-3 PG 6 WC Ophthalmology SC Ophthalmology GA 633PT UT WOS:000180292200031 PM 12511357 ER PT B AU Rice, KC AF Rice, KC BE Meldrum, ML TI Analgesic research at the National Institutes of Health: State of the art 1930s to the present SO OPIOIDS AND PAIN RELIEF: A HISTORICAL PERSPECTIVE SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT Symposium on Opioids and Pain Relief CY AUG 23-24, 2002 CL UNIV CALIF LOS ANGELES, LOS ANGELES, CA SP John C Liebeskind Hist Pain Collect HO UNIV CALIF LOS ANGELES ID RECEPTOR-MEDIATED PHENOMENA; HORMONE TYPE-1 RECEPTOR; CORTICOTROPIN-RELEASING-FACTOR; POSITRON-EMISSION-TOMOGRAPHY; OPIOID RECEPTOR; CANNABINOID RECEPTOR; (+)-4-<(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBE SNC-80; PERIPHERAL INFLAMMATION; (&)-MORPHINAN SERIES; PRACTICAL SYNTHESIS C1 NIDDKD, Med Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. NR 69 TC 1 Z9 1 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-47-7 J9 PROG PAIN RES MANAG PY 2003 VL 25 BP 57 EP 83 PG 27 WC Health Care Sciences & Services; History & Philosophy Of Science; Pharmacology & Pharmacy SC Health Care Sciences & Services; History & Philosophy of Science; Pharmacology & Pharmacy GA BX42W UT WOS:000185234900005 ER PT J AU Sowers, MR Finkelstein, JS Ettinger, B Bondarenko, I Neer, RM Cauley, JA Sherman, S Greendale, GA AF Sowers, MR Finkelstein, JS Ettinger, B Bondarenko, I Neer, RM Cauley, JA Sherman, S Greendale, GA TI The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE BMD; estradiol; FSH; menopause; menopause transition ID FOLLICLE-STIMULATING-HORMONE; PREMENOPAUSAL WOMEN; INHIBIN-B; PHYSICAL-ACTIVITY; DIMERIC INHIBIN; RISK-FACTORS; MASS; OVARIAN; MENOPAUSE; ENDOCRINOLOGY AB We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 4252 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = -0.10 for lumbar spine [95% confidence interval (0): -0.13, -0.06] and r = -0.08 for femoral neck (95% Cl: -0.11, -0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multi-ethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period. C1 Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Div Geriatr, Sch Med, Los Angeles, CA USA. RP Sowers, MR (reprint author), Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Rm 3073,SPH-1,109 Observ St, Ann Arbor, MI 48109 USA. RI Perez , Claudio Alejandro/F-8310-2010; Cauley, Jane/N-4836-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [U01 AG12531, U01 AG12495, U01 AG12546, U01 AG12553, U01 AG12554, U01 AG2539]; NINR NIH HHS [U01 NR04061] NR 40 TC 62 Z9 63 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2003 VL 14 IS 1 BP 44 EP 52 DI 10.1007/s00198-002-1307-x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 650FA UT WOS:000181251200007 PM 12577184 ER PT J AU Russo, CR Lauretani, F Bandinelli, S Bartali, B Di Iorio, A Volpato, S Guralnik, JM Harris, T Ferrucci, L AF Russo, CR Lauretani, F Bandinelli, S Bartali, B Di Iorio, A Volpato, S Guralnik, JM Harris, T Ferrucci, L TI Aging bone in men and women: beyond changes in bone mineral density SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE bone mechanical properties; elderly; osteoporosis; pQCT ID QUANTITATIVE COMPUTED-TOMOGRAPHY; INACCURACIES INHERENT; FRACTURE RISK; CORTICAL BONE; OSTEOPOROSIS; STRENGTH; PERSPECTIVE; DIAGNOSIS; FRAGILITY; SKELETON AB Using peripheral quantitative computed tomography (pQCT) we assessed trabecular and cortical bone density, mass and geometric distribution at the tibia level in 512 men and 693 women, age range 20102 years, randomly selected from the population living in the Chianti area, Tuscany, Italy. Total, trabecular and cortical bone density decreased linearly with age (p<<0.0001 in both sexes), and the slope of age-associated decline was steeper in women than in men. In men. the cortical bone area was similar in different age groups, while in women older than 60 years it was significantly smaller by approximately 1% per year. The total cross-sectional area of the bone became progressively wider with age, but the magnitude of the age-associated increment was significantly higher in men than in women (p<0.001). The minimum moment of inertia, an index of mechanical resistance to bending, remained stable with age in men, while it was significantly lower in older compared with younger women (0.5% per year). The increase in bone cross-sectional area in aging men may contribute to the maintenance of adequate bone mechanical competence in the face of declining bone density. In women this compensatory mechanism appears to be less efficient and, accordingly, the bone mechanical competence declines with age. The geometric adaptation of increasing cross-sectional bone size is an important component in the assessment of bone mechanical resistance which is completely overlooked, and potentially misinterpreted, by traditional planar densitometry. C1 INRCA, Dept Geriatr, Lab Clin Epidemiol, I-50127 Florence, Italy. Univ Florence, Dept Crit Care Med & Surg, Sect Gerontol & Geriatr Med, Florence, Italy. Univ Chieti, Dept Med & Aging, Chieti, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), INRCA, Dept Geriatr, Lab Clin Epidemiol, Viale Michelangiolo 41, I-50127 Florence, Italy. RI VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016 OI VOLPATO, STEFANO/0000-0003-4335-6034; Lauretani, Fulvio/0000-0002-5287-9972 FU NIMHD NIH HHS [263-MD-821336, 236-MD-9164-13] NR 31 TC 81 Z9 83 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2003 VL 14 IS 7 BP 531 EP 538 DI 10.1007/s00198-002-1322-y PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710QC UT WOS:000184690100001 PM 12827220 ER PT J AU Andriamanalijaona, R Felisaz, N Kim, SJ Pujol, JP Boumediene, K AF Andriamanalijaona, R Felisaz, N Kim, SJ Pujol, JP Boumediene, K TI AP-4 transcription factor mediates interleukin-1 beta-induced transforming growth factor beta 1 expression in articular chondrocytes SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 4th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ECCEO 4) CY NOV 14-17, 2003 CL NICE, FRANCE SP WHO Collaborat Ctr Public Hlth Aspects Osteoart Disorders, Int Osteoporosis Fdn C1 Fac Med, Lab Connect Tissue Biochem, F-14032 Caen, France. NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2003 VL 14 SU 7 BP S22 EP S22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 756ZJ UT WOS:000187515400059 ER PT J AU Young, MF AF Young, MF TI Bone matrix proteins: their function, regulation, and relationship to osteoporosis SO OSTEOPOROSIS INTERNATIONAL LA English DT Article; Proceedings Paper CT World Congress on Osteoporosis CY MAY 10, 2002 CL LISBON, PORTUGAL DE bone matrix proteins; collagens; noncollagenous proteins; osteoporosis ID GROWTH-FACTOR-BETA; CALVARIAL OSTEOBLAST DIFFERENTIATION; OSTEOCALCIN-DEFICIENT MICE; MARROW STROMAL CELLS; SP1 BINDING-SITE; EXTRACELLULAR-MATRIX; BIOCHEMICAL MARKERS; PARATHYROID-HORMONE; CROSS-LINKS; IN-VITRO AB Bone is a unique tissue composed of numerous cell types entombed within a mineralized matrix each with its own unique functions. While the majority of the matrix is composed of inorganic materials, study of the organic components has yielded most of the insights into the roles and regulation of cell and tissue specific functions. The goal of this review will be to describe some of the major known organic components of the bone matrix and discuss their functions as currently perceived. The potential usefulness of bone matrix protein assays for diagnosing the status of bone diseases and our current understanding of how these proteins could be related to diseases such as osteoporosis will also be reviewed. C1 NIDR, Craniofacial & Skeletal Dis Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Young, MF (reprint author), NIDR, Craniofacial & Skeletal Dis Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NR 93 TC 65 Z9 68 U1 1 U2 16 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2003 VL 14 SU 3 BP S35 EP S42 DI 10.1007/s00198-002-1342-7 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688VT UT WOS:000183458200007 PM 12730768 ER PT S AU Stein, W Subramanian, S Mitchell, JB Krishna, MC AF Stein, W Subramanian, S Mitchell, JB Krishna, MC BE Wilson, DF Evans, SY Biaglow, J Pastuszko, A TI EPR imaging of vascular changes in oxygen in response to carbogen breathing SO OXYGEN TRANSPORT TO TISSUE VOLUME XXIII: OXYGEN MEASUREMENTS IN THE 21ST CENTURY: BASIC TECHNIQUES AND CLINICAL RELEVANCE SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 29th Annual General Meeting of the International-Society-for-Oxygen-Transport-to-Tissue CY AUG 11-15, 2001 CL UNIV PENN, PHILADELPHIA, PENNSYLVANIA SP Int Soc Oxygen Transport Tissue, Alliance Pharmaceut Corp, AstraZeneca Pharmaceut Inc, Univ Penn, Inst Environm Med HO UNIV PENN C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47394-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 510 BP 231 EP 236 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BW13U UT WOS:000180978900038 PM 12580433 ER PT S AU Shonat, RD Koretsky, AP AF Shonat, RD Koretsky, AP BE Dunn, JF Swartz, HM TI Expression of myoglobin in the transgenic mouse brain SO OXYGEN TRANSPORT TO TISSUE XXIV SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the International-Society-on-Oxygen-Transport-to-Tissue CY AUG 28-SEP 02, 1999 CL DARTMOUTH MED SCH, HANOVER, NEW HAMPSHIRE SP Int Soc Oxygen Transport Tissue HO DARTMOUTH MED SCH DE blood flow; brain energetics; NMR perfusion imaging; NMR spectroscopy; oxygenation; transgenic mice ID PROMOTER; CLONING; OXYGEN; MICE; GENE; STIMULATION; PERFUSION; INVIVO; MUSCLE; PO2 AB The main purpose of this study was to express human myoglobin in mouse brain neurons and investigate the effects of this expression on metabolism and blood flow using phosphorous (P-31) NMR spectroscopy and NMR perfusion imaging. Transgenic mice expressing brain myoglobin were created using a cDNA sequence for human myoglobin placed under the transcriptional control of either a human platelet-derived grown factor polypeptide B (PDGF-B) promoter sequence or a rat neuron-specific enolase (NSE) promoter sequence. The presence of myoglobin having a functional, reduced-state, heme group was demonstrated by protein analysis and immunocytochemistry. Expression levels were highest in the hippocampus, cerebellum, and cerebral cortex. No gross morphological adaptations of neural tissue resulting from the expression were observed and no statistically significant differences in the energetic state, as measured by P-31 NMR, or baseline cortical perfusion, as measured by an NMR perfusion imaging technique, were found. C1 Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. NINDS, In Vivo NMR Res Ctr, NIH, Bethesda, MD 20892 USA. RP Shonat, RD (reprint author), Worcester Polytech Inst, Dept Biomed Engn, 100 Inst Rd, Worcester, MA 01609 USA. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NCRR NIH HHS [RR-03631]; NHLBI NIH HHS [HL-40354, HL-02847, HL-09418-02] NR 24 TC 7 Z9 7 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47774-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 530 BP 331 EP 345 PG 15 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA BX70X UT WOS:000186182800031 PM 14562729 ER PT S AU Okunieff, P Fenton, BM Zhang, LR Kern, FG Wu, T Greg, JR Ding, I AF Okunieff, P Fenton, BM Zhang, LR Kern, FG Wu, T Greg, JR Ding, I BE Dunn, JF Swartz, HM TI Fibroblast growth factors (FGFs) increase breast tumor growth rate, metastases, blood flow, and oxygenation without significant change in vascular density SO OXYGEN TRANSPORT TO TISSUE XXIV SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the International-Society-on-Oxygen-Transport-to-Tissue CY AUG 28-SEP 02, 1999 CL DARTMOUTH MED SCH, HANOVER, NEW HAMPSHIRE SP Int Soc Oxygen Transport Tissue HO DARTMOUTH MED SCH DE angiogenesis; hypoxia; fibroblast growth factor; blood flow; breast cancer ID NUDE-MICE; FACTOR-IV; ANGIOGENESIS AB Breast tumors expressing no detectable FGFs (MCF-7) were compared with tumors transfected with FGF4 or FGF1 (FGF4/MCF-7 or FGFI/MCF-7), and with MDA-MB-435, which produce endogenous FGF2. Tumor blood flow was measured by Xe-133 diffusion, oxygen distribution was measured by Eppendorf pO(2) histography, and vascular density was measured by CD31 staining. Tumors that overexpress angiogenic factors grew at a rate far exceeding that of MCF-7. The FGF producing tumors also had much higher metastatic rates to lung. Tumor blood flow was significantly higher in the two FGF-transfected xenografts compared with the parent MCF7. Median tumor pO(2) was also higher, and tumor oxygenation was preserved even for large tumors. The vascular density as determined by CD31 staining, however, was not markedly increased in tumors overexpressing angiogenic factors. We found that angiogenic factors preserve and augment neovascular function, thus facilitating tumor growth and progression. C1 Univ Rochester, Dept Radiat Oncol, Rochester, NY 14627 USA. Georgetown Univ, Dept Cellular & Mol Biol, Washington, DC USA. So Res Inst, Birmingham, AL 35255 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Okunieff, P (reprint author), Univ Rochester, Dept Radiat Oncol, Rochester, NY 14627 USA. NR 11 TC 17 Z9 18 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47774-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 530 BP 593 EP 601 PG 9 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA BX70X UT WOS:000186182800058 PM 14562756 ER PT B AU Zhang, S Bodenreider, O AF Zhang, S Bodenreider, O BE Altman, RB Dunker, AK Hunter, L Jung, TA Klein, TE TI Investigating implicit knowledge in ontologies with application to the anatomical domain SO PACIFIC SYMPOSIUM ON BIOCOMPUTING 2004 LA English DT Proceedings Paper CT Pacific Symposium on Biocomputing (PSB) CY JAN 06-10, 2004 CL HI AB Knowledge in biomedical ontologies can be explicitly represented (often by means of semantic relations), but may also be implicit, i.e., embedded in the concept names and inferable from various combinations of semantic relations. This paper investigates implicit knowledge in two ontologies of anatomy: the Foundational Model of Anatomy and GALEN. The methods consist of extracting the knowledge explicitly represented, acquiring the implicit knowledge through augmentation and inference techniques, and identifying the origin of each semantic relation. The number of relations (12 million in FMA and 4.6 million in GALEN), broken down by source, is presented. Major findings include! each technique provides specific relations; and many relations can be generated by more than one technique. The application of these findings to ontology auditing, validation, and maintenance is discussed, as well as the application to ontology integration. C1 US Natl Lib Med, Bethesda, MD 20894 USA. RP US Natl Lib Med, 8600 Rockville Pike,MS 43, Bethesda, MD 20894 USA. EM szhang@nlm.nih.gov; olivier@nlm.nih.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-598-3 PY 2003 BP 250 EP 261 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BCM65 UT WOS:000230001500021 ER PT J AU Costantini, M Higginson, IJ Boni, L Orengo, MA Garrone, E Henriquet, F Bruzzi, P AF Costantini, M Higginson, IJ Boni, L Orengo, MA Garrone, E Henriquet, F Bruzzi, P TI Effect of a palliative home care team on hospital admissions among patients with advanced cancer SO PALLIATIVE MEDICINE LA English DT Article DE cancer; effectiveness; evaluation; home care; palliative care ID RANDOMIZED CONTROLLED TRIAL; TERMINALLY ILL; COST-EFFECTIVENESS; NATIONAL HOSPICE; SERVICE; SAVINGS; LIFE AB This was a quasi-experimental study designed to determine whether, in patients with advanced cancer, a palliative home care team (PHCT) modified hospital utilization in the last six months before death. Of 2503 cancer deaths in the municipality of Genoa, Italy, in 1991, 189 (7.5%) received care from a PHCT. Three hundred and seventy-eight controls matched for primary tumour were selected. The groups were similar in terms of age, gender and most other demographic variables, except that educational level was lower, and times to death, from first diagnosis and from diagnosis of advanced or metastatic cancer, were longer among PHCT patients compared with the controls. Before referral to a PHCT, or a matched time in controls, both groups spent about 15% of days in hospital. After admission to a PHCT, the percentages of days in hospital increased in both groups as death approached, but it was much higher in the control group (30.3%; 95% confidence interval (CI): 26-34) than in the PHCT group (19.0%; 95% CI: 15-23). The difference between groups was most marked in the last month of life, and disappeared among those patients who were in care for more than 120 days (throughout the course of their illness). We conclude that a PHCT appears to reduce days in hospital and allows patients to spend more time at home. Differences in time in care between groups requires further investigations. C1 Natl Canc Inst, Unit Clin Epidemiol & Trials, I-16132 Genoa, Italy. Kings Coll London, Dept Palliat Care & Policy, London, England. CBA, Assoc BETA, Genoa, Italy. Natl Canc Inst, Canc Registry Sect, Genoa, Italy. Natl Canc Inst, Mortal Registry Sect, Genoa, Italy. G Ghirotti Assoc Res & Treatment Pain & Palliat C, Genoa, Italy. Natl Canc Inst, Unit Clin Epidemiol & Trials, Genoa, Italy. RP Costantini, M (reprint author), Natl Canc Inst, Unit Clin Epidemiol & Trials, L go R Benzi 10, I-16132 Genoa, Italy. EM costantini@cba.unige.it RI costantini, massimo/G-1443-2012; OI costantini, massimo/0000-0002-5293-7079; Bruzzi, Paolo/0000-0002-7874-2077 NR 23 TC 38 Z9 38 U1 0 U2 5 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PY 2003 VL 17 IS 4 BP 315 EP 321 DI 10.1191/0269216303pm744oa PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 683LZ UT WOS:000183152100004 PM 12822847 ER PT J AU Bornstein, MH Hendricks, C Hahn, CS Haynes, OM Painter, KM Tamis-LeMonda, CS AF Bornstein, Marc H. Hendricks, Charlene Hahn, Chun-Shin Haynes, O. Maurice Painter, Kathleen M. Tamis-LeMonda, Catherine S. TI Contributors to Self-Perceived Competence, Satisfaction, Investment, and Role Balance in Maternal Parenting: A Multivariate Ecological Analysis SO PARENTING-SCIENCE AND PRACTICE LA English DT Article AB Objective. This study employed an ecological framework to examine the roles of multiple contributors to variations in key maternal perceptions of their own parenting. Design. Maternal socioeconomic status (SES), employment, and parenting support; child gender, language, social competence, and temperament; and maternal intelligence, personality, and parenting knowledge and style were explored in separate predictions of self-perceived competence, satisfaction, investment, and role balance in 234 European American mothers of firstborn, 20-month-old children. Results. Hierarchical regression analyses indicated highly differentiated patterns of unique predictive relations to each domain of self-perceived parenting. Nonetheless, some predictors consistently contributed to individual parenting self-perceptions, most prominently, parenting knowledge and dissonance between actual and ideal maternal and paternal parenting styles. SES, maternal employment, community support, and maternal personality also contributed to self-perceptions, as did child temperament. Conclusions. Although the potential contributors to parenting self-perceptions may be many, prominent contributors to any one self-perception are few, and constellations of contributors differ for different parenting self-perceptions, conclusions that articulate with the modular view of parenting. C1 [Bornstein, Marc H.] NICHHD, Bethesda, MD 20892 USA. [Hendricks, Charlene; Hahn, Chun-Shin; Haynes, O. Maurice; Painter, Kathleen M.] NICHD, Bethesda, MD USA. [Tamis-LeMonda, Catherine S.] NYU, New York, NY 10003 USA. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 178 TC 30 Z9 31 U1 0 U2 9 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2003 VL 3 IS 4 BP 285 EP 326 AR PII 785828798 DI 10.1207/s15327922par0304_2 PG 42 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA V12OY UT WOS:000207609700002 ER PT S AU Hallett, M AF Hallett, M BE Gordin, A Kaakkola, S Teravainen, H TI Parkinson revisited: Pathophysiology of motor signs SO PARKINSON'S DISEASE SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 14th International Congress on Parkinsons Disease CY JUL 28-31, 2001 CL HELSINKI, FINLAND ID TRANSCRANIAL MAGNETIC STIMULATION; RECIPROCAL INHIBITION; ESSENTIAL TREMOR; STRETCH REFLEX; REACTION-TIME; ELECTRICAL-STIMULATION; VOLUNTARY MOVEMENT; H-REFLEX; DISEASE; RIGIDITY C1 Natl Inst Neurol Dis Ctr, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), Natl Inst Neurol Dis Ctr, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 72 TC 32 Z9 33 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 BN 0-7817-4084-3 J9 ADV NEUROL JI Adv.Neurol. PY 2003 VL 91 BP 19 EP 28 PG 10 WC Genetics & Heredity; Clinical Neurology; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA BV64Y UT WOS:000179636000003 PM 12442661 ER PT S AU Blanchet, PJ Metman, LV Chase, TN AF Blanchet, PJ Metman, LV Chase, TN BE Gordin, A Kaakkola, S Teravainen, H TI Renaissance of amantadine in the treatment of Parkinson's disease SO PARKINSON'S DISEASE SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 14th International Congress on Parkinsons Disease CY JUL 28-31, 2001 CL HELSINKI, FINLAND ID LEVODOPA-INDUCED DYSKINESIAS; MOTOR RESPONSE ALTERATIONS; NMDA RECEPTOR BLOCKADE; DOUBLE-BLIND; OLD DRUG; FLUCTUATIONS; ANTAGONISTS; MONKEYS; BRAIN; NEUROTOXICITY C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ Montreal, Fac Dent, Montreal, PQ, Canada. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. RP Blanchet, PJ (reprint author), NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 44 TC 44 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 BN 0-7817-4084-3 J9 ADV NEUROL JI Adv.Neurol. PY 2003 VL 91 BP 251 EP 257 PG 7 WC Genetics & Heredity; Clinical Neurology; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA BV64Y UT WOS:000179636000026 PM 12442683 ER PT S AU Hardy, J AF Hardy, J BE Federoff, HJ Burke, RE Fahn, S Fiskum, G TI The relationship between Lewy body disease, Parkinson's disease, and Alzheimer's disease SO PARKINSON'S DISEASE: THE LIFE CYCLE OF THE DOPAMINE NEURON SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Parkinsons Disease - The Life Cycle of the Dopamine Neuron CY SEP 18-20, 2002 CL PRINCETON, NEW JERSEY SP New York Acad Sci DE Lewy body disease; Parkinson's disease; Alzheimer's disease ID AMYLOID PRECURSOR PROTEIN; PROGRESSIVE SUPRANUCLEAR PALSY; ALPHA-SYNUCLEIN; BRAIN PATHOLOGY; DEMENTIA; BODIES; TAU; GENE; MUTATIONS; MISSENSE AB The nosological relationship between Parkinson's disease, dementing syndromes with Lewy bodies, and Alzheimer's disease has been the subject of continuing debate. Here I argue, on the basis of recent data from families with hereditary versions of these diseases and from transgenic modeling, that these nosological debates are inevitable, impossible to resolve, and a product of the fact that we define diseases as entities rather than processes. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10,Room 6C103,MSC1589, Bethesda, MD 20892 USA. NR 29 TC 11 Z9 13 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-448-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 991 BP 167 EP 170 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BX10S UT WOS:000184302100017 PM 12846985 ER PT B AU Young, NS Maciejewski, JP Sloand, E Chen, G Zeng, WH Risitano, A Miyazato, A AF Young, NS Maciejewski, JP Sloand, E Chen, G Zeng, WH Risitano, A Miyazato, A BE Omine, M Kinoshita, T TI The enigma of the aplastic anemia/PNH syndrome SO PAROXYSMAL NOCTURNAL HEMOGLOBINURIA AND RELATED DISORDERS: MOLECULAR ASPECTS OF PATHOGENESIS LA English DT Proceedings Paper CT International Symposium on Paroxysmal Nocturnal Hemoglobinuria and Related Disorders CY AUG 29, 2001 CL TOKYO, JAPAN SP Japan Intractable Dis Res Fdn, Res Comm Indiopath Hematopoiet Disorders, Minist Hlth, Labour & Welfare Japan, Japanese Soc Hematol, Japanese Soc Clin Hematol ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; PIG-A GENE; T-CELL REPERTOIRE; BONE-MARROW; ANCHORED PROTEINS; SOMATIC MUTATIONS; MUTANT-CELLS; DEFICIENT; HEMATOPOIESIS; CYCLOSPORINE AB Bone marrow failure has been regarded as one consequence of paroxysmal nocturnal hemoglobinuria (PNH), and PNH in turn has been described as a late event in patients recovering from aplastic anemia. Better understanding of the pathophysiology of both diseases and improved tests for cell surface glycosylphosphatidylinositol (GPI)-linked proteins have radically altered this view. How cytometry of granulocytes shows evidence of an expanded PNH clone in a large proportion of marrow failure patients at the time of presentation: in our large NIH series, about 1/3 of over 200 aplastic anemia cases and almost 20% of more than 100 myclodysplasia cases. Clonal PNH expansion (rather than bone marrow failure) is strongly linked to the histocompatability antigen H.A.-DR2 in all clinical varieties of the disease, suggesting a relationship to the immune pathophysiology. An extrinsic mechanism of clonal expansion is also more consistent with knock-out mouse models and culture experiments with primary cells and cell lines, which have failed to demonstrate an intrinsic proliferative advantage for PNH cells. DNA chip analysis of multiple paired normal and PIGA mutant cell lines and lymphoblastoid cells do not show any consistent differences in levels of gene expression. In aplastic anemia/PNH there is surprisingly limited utilization of the Vbeta chain of the T cell receptor, and patients' dominant T cell clones, which are functionally inhibitory of autologous hematopoiesis, use identical CDR3 regions for antigen binding. Phenotypically normal cells from PNH patients proliferate more poorly in culture than do the same patient's PNH cells, and the normal cells are damaged as a result of apoptosis and overexpress Fas. Differences in protein degradation might play a dual role in pathophysiology, as GPI-linked proteins lacking an anchor would be predicted to be processed by the proteasome machinery and displayed in a class I HLA. context, in contrast to the normal pathway of cell surface membrane recycling, lysosomal degradation, and presentation by class II HLA. In summary, the strong relationship of a chronic, organ-specific immune destructive process and the expansion of a single mutant stem cell clone remains frustratingly enigmatic but likely to be the result of unusual and interesting biology. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103, Bethesda, MD 20892 USA. NR 39 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-70329-2 PY 2003 BP 149 EP 158 PG 10 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA BW11M UT WOS:000180924600014 ER PT J AU Holland, SM AF Holland, SM TI Update on phagocytic defects SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Editorial Material ID CHRONIC GRANULOMATOUS-DISEASE; ECTODERMAL DYSPLASIA; MYCOBACTERIAL; IMPAIRMENT; IMMUNITY C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2003 VL 22 IS 1 BP 87 EP 88 DI 10.1097/00006454-200301000-00020 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 636KY UT WOS:000180455900015 PM 12544415 ER PT J AU Brodie, SG Deng, CX AF Brodie, SG Deng, CX TI Mouse models orthologous to FGFR3-related skeletal dysplasias SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Article DE achondroplasia; FGFR3; gene targeting; hypochondroplasia; mouse models; skeletal development; skeletal dysplasia; thanatophoric dysplasia ID GROWTH-FACTOR RECEPTOR; IMMUNOGLOBULIN-LIKE DOMAIN; THANATOPHORIC DYSPLASIA; TRANSMEMBRANE DOMAIN; CONSTITUTIVE ACTIVATION; EXTRACELLULAR DOMAIN; TRANSCRIPTION FACTOR; CROUZON SYNDROME; FIBROBLAST; MUTATIONS AB Fibroblast growth factor receptor 3 (FGFR3) is one of the membrane bound tyrosine kinases that mediate the actions of fibroblast growth factor (FGF) family members. Missense mutations in the coding regions of FGFR3 have been identified in allelic forms of short-limbed dwarfism. Using gene targeting, we demonstrated that Fgfr3 plays an essential role in endochondral ossification and that a loss-of-function mutation causes accelerated and prolonged long bone growth. Using a number of molecular genetic approaches, we also have introduced into the mouse genome a series of mutations that correspond to the missense mutations identified in individuals with achondroplasia and thanatophoric dysplasia. These mouse models mimic the human condition and can be used for further studies to identify and characterize in vivo changes associated with various Fgfr3 mutations. In additions, these models may be beneficial in future studies to attempt novel treatment strategies for short-limbed dwarfism. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brodie, SG (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 68 TC 14 Z9 15 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD JAN-FEB PY 2003 VL 22 IS 1 BP 87 EP 103 DI 10.1080/15227950390168200 PG 17 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 630NN UT WOS:000180114700009 PM 12687892 ER PT J AU Savage, SA Chanock, S AF Savage, SA Chanock, S TI Genetic variation and hematopoietic stem cell transplantation: expansion of the paradigm SO PEDIATRIC TRANSPLANTATION LA English DT Article; Proceedings Paper CT Meeting on Marrow Transplantation in Children: Current Results and Controversies CY NOV 08-10, 2001 CL ST AUGUSTINE, FL ID SINGLE-NUCLEOTIDE POLYMORPHISMS; BONE-MARROW-TRANSPLANTATION; MANNOSE-BINDING LECTIN; VERSUS-HOST-DISEASE; HUMAN GENOME; HIV-1 INFECTION; HLA SYSTEM; 2 PARTS; ASSOCIATION; SEVERITY AB Genetic variation has been the mainstay of hematopoietic stem cell transplantation since the first transplants were attempted. A significant expansion of genetic knowledge is under way, as the draft sequence of the human genome is annotated. Hematopoietic stem cell transplantation is a field that will greatly benefit from this new knowledge, but the manner in which it is applied is daunting. Variation within key molecules related to hematopoietic stem cell transplant in combination with the current knowledge of human leukocyte antigen variation will serve to improve donor-recipient matches and clinical outcome. C1 NCI, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD 20877 USA. RP Chanock, S (reprint author), NCI, Pediat Oncol Branch, Ctr Adv Technol, 8717 Grovement Circle, Gaithersburg, MD 20877 USA. EM chanocks@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 40 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2003 VL 7 SU 3 BP 32 EP 39 DI 10.1034/j.1399-3046.7.s3.4.x PG 8 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 647DT UT WOS:000181077700005 PM 12603690 ER PT J AU Orlic, D Kajstura, J Chimenti, S Bodine, DM Leri, A Anversa, P AF Orlic, D Kajstura, J Chimenti, S Bodine, DM Leri, A Anversa, P TI Bone marrow stem cells regenerate infarcted myocardium SO PEDIATRIC TRANSPLANTATION LA English DT Article; Proceedings Paper CT Meeting on Marrow Transplantation in Children: Current Results and Controversies CY NOV 08-10, 2001 CL ST AUGUSTINE, FLORIDA DE stem cells; myocardial infarcts; cytokines; immunohistochemistry ID EXPRESSION; REPAIR; HEART; BLOOD; BRAIN; MICE AB Heart disease is the leading cause of death in the United States for both men and women. Nearly 50% of all cardiovascular deaths result from coronary artery disease. Occlusion of the left coronary artery leads to ischemia, infarction, necrosis of the affected myocardial tissue followed by scar formation and loss of function. Although myocytes in the surviving myocardium undergo hypertrophy and cell division occurs in the border area of the dead tissue, myocardial infarcts do not regenerate and eventually result in the death of the individual. Numerous attempts have been made to repair damaged myocardium in animal models and in humans. Bone marrow stem cells (BMSC) retain the ability throughout adult life to self-renew and differentiate into cells of all blood lineages. These adult BMSC have recently been shown to have the capacity to differentiate into multiple specific cell types in tissues other than bone marrow. Our research is focused on the capacity of BMSC to form new cardiac myocytes and coronary vessels following an induced myocardial infarct in adult mice. In this paper we will review the data we have previously published from studies on the regenerative capacity of BMSC in acute ischemic myocardial injury. In one experiment donor BMSC were injected directly into the healthy myocardium adjacent to the injured area of the left ventricle. In the second experiment, mice were treated with cytokines to mobilize their BMSC into the circulation on the theory that the stem cells would traffic to the myocardial infarct. In both experimental protocols, the BMSC gave rise to new cardiac myocytes and coronary blood vessels. This BMSC-derived myocardial regeneration resulted in improved cardiac function and survival. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. RP Orlic, D (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 3W16,49 Convent Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL 38132, HL 39902, HL 43023, HL 65577, HL 66923]; NIA NIH HHS [AG 15756, AG 17042] NR 14 TC 160 Z9 183 U1 3 U2 22 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2003 VL 7 SU 3 BP 86 EP 88 DI 10.1034/j.1399-3046.7.s3.13.x PG 3 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 647DT UT WOS:000181077700014 PM 12603699 ER PT J AU Cheng, TL Brenner, RA Wright, JL Sachs, HC Moyer, P Rao, M AF Cheng, TL Brenner, RA Wright, JL Sachs, HC Moyer, P Rao, M TI Community norms on toy guns SO PEDIATRICS LA English DT Article DE toy gun play; violence prevention; anticipatory guidance; parental norms ID CHILDREN; BELIEF; PLAY AB Objective. Toy gun play has been associated with aggressive behavior, and it has been suggested that child health professionals counsel families on limiting exposure. Effective violence prevention counseling requires an understanding of norms regarding parental attitudes, practices, and influencing factors. Both theories of reasoned action and planned behavior emphasize that subjective norms and attitudes affect people's perceptions and intended behavior. Few normative data exist on this issue from a cross-section of families. By establishing behavioral norms and understanding the spectrum of parental attitudes, community-sensitive and community-specific interventions for violence prevention can be developed. The objective of this study was to assess community norms on the topic of toy gun play from the perspective of parents. Methods. An anonymous self-report assisted survey was administered to a convenience sample of parents/guardians who visited child health providers at 3 sites: an urban children's hospital clinic, an urban managed care clinic, and a suburban private practice. The parent questionnaire included questions on child rearing attitudes, practice, and sociodemographic information. Results. A total of 1004 eligible participants were recruited for the study; 922 surveys were completed (participation rate 92%). The 830 (90%) respondents who were parents and had complete child data were the focus of additional analysis. Regarding toy guns, 67% of parents believed that it was never "OK for a child to play with toy guns," and 66% stated that they never let their children play with toy guns. Parents who thought that it was okay for children to play with toy guns and allowed them to play with toy guns were more likely to be male parents, have male children, and be white. Conclusions. There is variability in norms regarding toy gun play among parents, with most discouraging toy gun play. Norms varied based on gender of the child, gender of the parent, and race. Understanding norms is a first step in designing effective community-sensitive interventions. C1 Childrens Natl Med Ctr, Dept Gen Pediat & Adolescent Med, Washington, DC 20010 USA. Childrens Res Inst, Washington, DC USA. George Washington Univ, Sch Med, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Emergency Med, Washington, DC 20010 USA. Coleman Sachs & Thillairajah Pediat, Rockville, MD USA. RP Cheng, TL (reprint author), Johns Hopkins Univ, Dept Gen Pediat & Adolescent Med, 600 N Wolfe St,Pk 392, Baltimore, MD 21287 USA. NR 26 TC 5 Z9 5 U1 2 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2003 VL 111 IS 1 BP 75 EP 79 DI 10.1542/peds.111.1.75 PG 5 WC Pediatrics SC Pediatrics GA 630XC UT WOS:000180135200028 PM 12509557 ER PT J AU Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMmillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Swanson, J Embree, J Fischer, MA Mahoney, M Gellin, BG Makhene, M Orenstein, WA Pratt, DR Starke, JR Pickering, LK Ledbetter, EO Cook, M AF Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMmillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Swanson, J Embree, J Fischer, MA Mahoney, M Gellin, BG Makhene, M Orenstein, WA Pratt, DR Starke, JR Pickering, LK Ledbetter, EO Cook, M CA Comm Infect Dis TI Recommended childhood and adolescent immunization schedule - United States, 2003 SO PEDIATRICS LA English DT Article C1 Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. Amer Acad Pediat, Pediat Practice Act Grp, Elk Grove Village, IL 60007 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Amer Acad Family Phys, Leawood, KS 66211 USA. Natl Vaccine Program Off, Atlanta, GA USA. NIH, Bethesda, MD 20892 USA. US FDA, Washington, DC 20204 USA. Amer Thorac Soc, New York, NY 10019 USA. RP Abramson, JS (reprint author), Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. NR 3 TC 11 Z9 11 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2003 VL 111 IS 1 BP 212 EP 212 PG 1 WC Pediatrics SC Pediatrics GA 630XC UT WOS:000180135200051 ER PT J AU Sanger, TD Delgado, MR Gaebler-Spira, D Hallett, M Mink, JW AF Sanger, TD Delgado, MR Gaebler-Spira, D Hallett, M Mink, JW CA Task Force Childhood Motor Disorde TI Classification and definition of disorders causing hypertonia in childhood SO PEDIATRICS LA English DT Article DE spasticity; dystonia; rigidity; movement disorders; hypertonia; pediatric; childhood ID MODIFIED ASHWORTH SCALE; HEMIPLEGIC CEREBRAL-PALSY; STRETCH REFLEX THRESHOLD; SPINAL-CORD INJURY; SPASTIC HYPERTONIA; INTERRATER RELIABILITY; RECIPROCAL EXCITATION; MUSCLE CONTRACTURE; MOTOR FUNCTION; CHILDREN AB Objective. This report describes the consensus outcome of an interdisciplinary workshop that was held at the National Institutes of Health in April 2001. The purpose of the workshop and this article are to define the terms "spasticity," "dystonia," and "rigidity" as they are used to describe clinical features of hypertonia in children. The definitions presented here are designed to allow differentiation of clinical features even when more than 1 is present simultaneously. Methods. A consensus agreement was obtained on the best current definitions and their application in clinical situations. Results. "Spasticity" is defined as hypertonia in which 1 or both of the following signs are present: 1) resistance to externally imposed movement increases with increasing speed of stretch and varies with the direction of joint movement, and/or 2) resistance to externally imposed movement rises rapidly above a threshold speed or joint angle. "Dystonia" is defined as a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. "Rigidity" is defined as hypertonia in which all of the following are true: 1) the resistance to externally imposed joint movement is present at very low speeds of movement, does not depend on imposed speed, and does not exhibit a speed or angle threshold; 2) simultaneous co-contraction of agonists and antagonists may occur, and this is reflected in an immediate resistance to a reversal of the direction of movement about a joint; 3) the limb does not tend to return toward a particular fixed posture or extreme joint angle; and 4) voluntary activity in distant muscle groups does not lead to involuntary movements about the rigid joints, although rigidity may worsen. Conclusion. We have provided a set of definitions for the purpose of identifying different components of childhood hypertonia. We encourage the development of clinical rating scales that are based on these definitions, and we encourage research to relate the degree of hypertonia to the degree of functional ability, change over time, and societal participation in children with motor disorders. C1 Stanford Univ, Med Ctr, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Texas Scottish Rite Hosp Children, Dept Neurol & Neurosci, Dallas, TX 75219 USA. Rehabil Inst Chicago, Dept Pediat, Chicago, IL 60611 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Dept Child Neurol, Rochester, NY 14642 USA. RP Sanger, TD (reprint author), Stanford Univ, Med Ctr, Dept Child Neurol, 300 Pasteur Dr,MS 5235, Stanford, CA 94305 USA. NR 64 TC 204 Z9 206 U1 2 U2 24 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2003 VL 111 IS 1 AR e89 DI 10.1542/peds.111.1.e89 PG 9 WC Pediatrics SC Pediatrics GA 630XC UT WOS:000180135200015 PM 12509602 ER PT J AU Moody, TW Hill, JM Jensen, RT AF Moody, TW Hill, JM Jensen, RT TI VIP as a trophic factor in the CNS and cancer cells SO PEPTIDES LA English DT Review DE VIP; CNS; cancer; development; proliferation ID VASOACTIVE-INTESTINAL-PEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; DEPENDENT NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR; MURINE DEVELOPING BRAIN; CULTURED SCHWANN-CELLS; HIGH-AFFINITY BINDING; NERVE GROWTH-FACTOR; PROTEIN-KINASE-C; ADENYLATE-CYCLASE AB The effects of vasoactive intestinal peptide (VIP) on the proliferation of central nervous system (CNS) and cancer cells were investigated. VIP has important actions during CNS development. During neurogenesis, VIP stimulates the proliferation and differentiation of brain neurons. Addition of VIP to embryonic mouse spinal cord cultures increases neuronal survival and activity dependent neurotrophic factor (ADNF) secretion from astroglial cells. VIP is an integrative regulator of brain growth and development during neurogenesis and embryogenesis. Also, VIP causes increased proliferation of human breast and lung cancer cells in vitro. VIP binds with high affinity to cancer cells, elevates the cAMP and increases gene expression of c-fos, c-jun, c-myc and vascular endothelial cell growth factor. The effects of VIP on cancer cells are reversed by VIPhybrid, a synthetic VPAC(1) receptor antagonist. VIPhyb inhibits the basal growth of lung cancer cells in vitro and tumors in vivo and potentiates the ability of chemotherapeutic drugs to kill cancer cells. Due to the high density of VPAC(1) receptors in cancer cells, VIP has been radiolabeled with I-123, F-18 and Tc-99m to image tumors. It remains to be determined if radiolabeled VIP analogs will be useful agents for early detection of cancer in patients. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NCI, Off Director, Ctr Canc Res, Bethesda, MD 20892 USA. NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. RP NCI, Off Director, Ctr Canc Res, Bldg 31,Rm 3A34,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 187 TC 69 Z9 73 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD JAN PY 2003 VL 24 IS 1 BP 163 EP 177 DI 10.1016/S0196-9781(02)00290-5 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 650LG UT WOS:000181264700021 PM 12576099 ER PT J AU Watanabe, K Sato, TR Shimojo, S AF Watanabe, K Sato, TR Shimojo, S TI Perceived shifts of flashed stimuli by visible and invisible object motion SO PERCEPTION LA English DT Article ID PURSUIT EYE-MOVEMENTS; DISTORTS VISUAL SPACE; APPARENT MOTION; REPETITION BLINDNESS; LOCALIZATION ERRORS; POSITION; ATTENTION; PERCEPTION; FEATURES; DISPLACEMENT AB Perceived positions of flashed stimuli can be altered by motion signals in the visual field-position capture (Whitney and Cavanagh, 2000 Nature Neuroscience 3 954-959). We examined whether position capture of flashed stimuli depends on the spatial relationship between moving and flashed stimuli, and whether the phenomenal permanence of a moving object behind an occluding surface (tunnel effect; Michotte 1950 Acta Psychologica 7 293-322) can produce position capture. Observers saw two objects (circles) moving vertically in opposite directions, one in each visual hemifield. Two horizontal bars were simultaneously flashed at horizontally collinear positions with the fixation point at various timings. When the movement of the object was fully visible, the flashed bar appeared shifted in the motion direction of the circle. But this position-capture effect occurred only when the bar was presented ahead of or on the moving circle. Even when the motion trajectory was covered by an opaque surface and the bar was flashed after complete occlusion of the circle, the position-capture effect was still observed, though the positional asymmetry was less clear. These results show that movements of both visible and 'hidden' objects can modulate the perception of positions of flashed stimuli and suggest that a high-level representation of 'objects in motion' plays an important role in the position-capture effect. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Psychol, Nashville, TN 37201 USA. CALTECH, Pasadena, CA 91125 USA. NTT Corp, NTT Commun Sci Labs, Atsugi, Kanagawa 2430198, Japan. RP Watanabe, K (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. NR 59 TC 27 Z9 27 U1 1 U2 3 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2003 VL 32 IS 5 BP 545 EP 559 DI 10.1068/p5047 PG 15 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 701GM UT WOS:000184159900003 PM 12854641 ER PT J AU Ruiz, MC Portero-Otin, M Pamplona, R Requena, JR Prat, J Lafarga, MA Borras, M Bellmunt, MJ AF Ruiz, MC Portero-Otin, M Pamplona, R Requena, JR Prat, J Lafarga, MA Borras, M Bellmunt, MJ TI Chemical and immunological characterization of oxidative nonenzymatic protein modifications in dialysis fluids SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article DE glycoxidation; lipoxidation; metalcatalyzed oxidation; pyrraline; N-epsilon-carboxymethyllysine; semialdehydes; aminoguanidine; free-radical production ID GLYCATION END-PRODUCTS; AMBULATORY PERITONEAL-DIALYSIS; ADVANCED MAILLARD REACTION; IN-VIVO; DIABETIC COMPLICATIONS; HEAT-STERILIZATION; UREMIC PATIENTS; CROSS-LINKING; N-EPSILON-(CARBOXYMETHYL)LYSINE; PYRRALINE AB Background: Glucose degradation products (GDP) in dialysis fluids may induce nonenzymatic protein modifications, the chemical nature and biological properties of which should be better defined. Aims: To characterize nonenzymatic protein modifications present in glucose-based peritoneal dialysis fluids (PDF) and to evaluate the relationship between concentrations of GDP and the derived nonenzymatic modifications, and the potential of PDF for generating these modifications in vitro. Methods: The presence, distribution, and content of several nonenzymatic protein modifications in PDF were evaluated by immunological methods, by HPLC, and by gas chromatography-mass spectrometry (GC/MS). Pertoneal dialysis fluid-induced oxidative stress in cells was evaluated by flow cytometry. The potential of PDF for generating oxidative and glycoxidative modifications was examined by immunological and cross-linking analyses. Results: The albumin present in PDF is modified by carboxymethyllysine (CML). GC/MS analyses of PDF proteins confirmed the presence of CIVIL and demonstrated the occurrence of carboxyethyllysine, malondialdehyde lysine, and oxidation-derived semialdehydes. Furthermore, their concentrations in PDF proteins were significantly higher than those in plasma proteins (in all cases, p < 0.02). The concentration of pyrraline, a non-oxidative advanced glycation end-product, increased with dwell time up to 6 hours (p < 0.03). The PDF induced cellular freeradical production, which was partially inhibited by the Maillard reaction inhibitor aminoguanidine (p < 0.001). The potential to generate oxidative and glycoxidative modifications demonstrated an inverse relationship with dwell time (p < 0.05). The PDF was able to induce collagen crosslinking in a close relationship with GDP concentration. Conclusions: (1) PDF contains non-oxidative and several oxidative nonenzymatic protein modifications in higher concentrations than plasma. (2) Peritoneal dialysis fluid induces oxidative stress in vitro, which can be partially inhibited by aminoguanidine. (3) These properties are directly related to GDP concentration. (4) Peritoneal dialysis fluid is able to generate glycoxidative and oxidative damage to proteins in vitro in a dwell-time dependent fashion. C1 Univ Lleida, Dept Basic Med Sci, Metab Pathophysiol Res Grp, E-25198 Lleida, Spain. Univ Hosp Arnau de Vilanova, Serv Nephrol, E-25198 Lleida, Spain. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bellmunt, MJ (reprint author), Univ Lleida, Dept Basic Med Sci, Metab Pathophysiol Res Grp, Avda Rovira Roure 44, E-25198 Lleida, Spain. RI Portero-Otin, Manuel/B-7122-2009; Bellmunt Curco, Maria Josep/C-3784-2011; Prat Corominas, Joan/C-6420-2011; Pamplona, Reinald/A-7359-2010 OI Portero-Otin, Manuel/0000-0002-1823-0299; Bellmunt Curco, Maria Josep/0000-0002-3187-1576; Pamplona, Reinald/0000-0003-4337-6107 NR 36 TC 7 Z9 8 U1 0 U2 1 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD JAN-FEB PY 2003 VL 23 IS 1 BP 23 EP 32 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 657BZ UT WOS:000181646700003 PM 12691503 ER PT J AU Ireland, CM Aalbersberg, W Andersen, RJ Ayral-Kaloustian, S Berlinck, RGS Bernan, V Carter, G Churchill, ACL Clardy, J Concepcion, GP De Silva, ED Discafani, C Fojo, T Frost, P Gibson, D Greenberger, LM Greenstein, M Harper, MK Mallon, R Loganzo, F Nunes, M Poruchynsky, MS Zask, A AF Ireland, CM Aalbersberg, W Andersen, RJ Ayral-Kaloustian, S Berlinck, RGS Bernan, V Carter, G Churchill, ACL Clardy, J Concepcion, GP De Silva, ED Discafani, C Fojo, T Frost, P Gibson, D Greenberger, LM Greenstein, M Harper, MK Mallon, R Loganzo, F Nunes, M Poruchynsky, MS Zask, A TI Anticancer agents from unique natural products sources SO PHARMACEUTICAL BIOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Pharmacognosy CY JUL 12-16, 2003 CL Chapel Hill, NC SP Amer Soc Pharmacognosy DE natural products; antitumor agents; NCDDG; sponges; fungi; marine microorganisms; hemiasterlins; austocystins ID ACTIVATED PROTEIN-KINASE; CYCLIN-DEPENDENT KINASES; LINKED-IMMUNOSORBENT-ASSAY; GROWTH-FACTOR RECEPTOR; TUMOR-CELL LINES; IN-VIVO; MULTIDRUG-RESISTANCE; CYTOTOXIC PEPTIDES; TYROSINE KINASE; TRIPEPTIDE HEMIASTERLIN AB The National Cooperative Natural Products Drug Discovery Group (NCNPDDG) "Anticancer Agents from Unique Natural Products Sources, CA 67786" was first awarded in September 1995. The goal of the project is to discover and develop novel anticancer agents from a variety of natural products sources. The key accomplishments of this NCDDG which will be highlighted in this manuscript include: Development of tools to probe fungi for the production of novel natural products by DNA-based probes. Discovery that the majority of these fungi can produce natural products via nonribosomal peptide synthetases, polyketide synthases, or both - a much larger percentage than current culturing techniques reveal. Identification of the MDR-selective cytotoxic agent austocystin D, and use of a novel yeast deletion strain approach to help identify its molecular target(s). Identification of hemiasterlin and other naturally occurring analogs as potent antimitotic agents with excellent in vivo activity against human solid tumors in mouse models. Development of a total synthesis of hemiasterlin. The utilization of this methodology to provide the first SAR for the hemiasterlin family of antimitotic agents and to identify the synthetic analog HTI-286, which is being examined in clinical trials as an anticancer agent. To provided technology transfer, educational opportunities and compensation to countries of origin for collection and study of their natural product resources. This NCNPDDG program has provided funding to research programs at the University of the Philippines, The University of the South Pacific in the Fiji Islands, Colombo University in Sri Lanka, the Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Brazil, and the University of Papua New Guinea. C1 Univ Utah, Coll Pharm, Dept Med Chem, Salt Lake City, UT 84112 USA. Univ Philippines, Inst Marine Sci, Quezon City 1101, Philippines. Wyeth Pharmaceut, Chem & Screening Sci, Pearl River, NY USA. NCI, Bethesda, MD 20892 USA. Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. Univ British Columbia, Dept Earth & Ocean Sci, Vancouver, BC V6T 1Z1, Canada. Wyeth Pharmaceut, Oncol Res, Pearl River, NY USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Colombo, Dept Chem, Colombo, Sri Lanka. Univ Sao Paulo, Inst Quim Sao Carlos, BR-13560970 Sao Carlos, SP, Brazil. Univ S Pacific, Sch Pure & Appl Sci, Suva, Fiji. Cornell Univ, Boyce Thompson Inst, Ithaca, NY 14853 USA. ARS, USDA, Plant Protect Res Unit, US Plant Soil & Nutr Lab, Ithaca, NY 14853 USA. RP Ireland, CM (reprint author), Univ Utah, Coll Pharm, Dept Med Chem, 307 Skaggs Hall,30 S 2000 E, Salt Lake City, UT 84112 USA. EM cireland@pharm.utah.edu RI Berlinck, Roberto/G-4756-2010; OI Berlinck, Roberto/0000-0003-0118-2523; de Silva, E. Dilip/0000-0001-8822-7186 NR 83 TC 16 Z9 16 U1 0 U2 5 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2003 VL 41 SU S BP 15 EP 38 DI 10.1080/1388020039051742 PG 24 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 877RK UT WOS:000225587500004 ER PT J AU Crews, P Gerwick, WH Schmitz, FJ France, D Bair, KW Wright, AE Hallock, Y AF Crews, P Gerwick, WH Schmitz, FJ France, D Bair, KW Wright, AE Hallock, Y TI Molecular approaches to discover marine natural product anticancer leads - An update from a drug discovery group collaboration SO PHARMACEUTICAL BIOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Pharmacognosy CY JUL 12-16, 2003 CL Chapel Hill, NC SP Amer Soc Pharmacognosy ID HISTONE DEACETYLASE INHIBITORS; TRICHOSTATIN-A; DNA METHYLTRANSFERASE; SPONGE; METABOLITES; APOPTOSIS; TRAPOXIN; POTENT; AGENTS; PSAMMAPLYSILLA AB This paper outlines the results of a collaborative program begun in 1990 under the NIH National Cooperative Drug Discovery Group (NCDDG) program. It involves the unified research of a multi-institutional group from both academic and corporate laboratories. Our working hypothesis is that targets identified through basic molecular and cell biology studies are relevant for the treatment of human cancers. Thus, a broad range of primary biochemical assays have guided the examination of extracts obtained from marine organisms (both collected and cultured) and purified marine natural products. The goal is to discover small molecules effective against these biological targets. An ever-changing panel of assays focus on a number of cancer relevant targets associated with the cell cycle, signal transduction, angiogenesis or apoptosis. A massive library of materials has been assembled for evaluation in the screens and it consists of more than 900 compounds and 16,000 extracts. We believe that these samples have enormous potential for chemodiveristy and progress to date supports this contention. The first part of the paper focuses on highlights from the period 1995-1999. The two most important developments were that the bengamide and the psammaplin families provided important insights leading to the development of two compounds, LAF-389 and NVP-LAQ824. These were both advanced to Phase I anticancer clinical trials. A sampling of recent discoveries, including current leads in development is also discussed. Attention then turns to new technologies and strategies aimed at shortening the time interval from an initial lead candidate discovery to assessment of its future therapeutic potential. C1 Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. Univ Calif Santa Cruz, Inst Marine Sci, Santa Cruz, CA 95064 USA. Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA. Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA. Novartis Inst Biomed Res, Oncol Res Program, Summit, NJ 07901 USA. NCI, NIH, Bethesda, MD 20892 USA. Harbor Branch Oceanog Inst Inc, Div Biomed Res, Ft Pierce, FL 34969 USA. RP Crews, P (reprint author), Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. EM phil@chemistry.ucsc.edu NR 51 TC 20 Z9 21 U1 0 U2 6 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2003 VL 41 SU S BP 39 EP 52 DI 10.1080/1388020039051743 PG 14 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 877RK UT WOS:000225587500005 ER PT J AU Hallock, YF Cragg, GM AF Hallock, YF Cragg, GM TI National cooperative drug discovery groups (NCDDGs): A successful model for public private partnerships in cancer drug discovery SO PHARMACEUTICAL BIOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Pharmacognosy CY JUL 12-16, 2003 CL Chapel Hill, NC SP Amer Soc Pharmacognosy ID HISTONE DEACETYLASE; ANTITUMOR-ACTIVITY; NATURAL-PRODUCTS; BENGAMIDE-B; HEMIASTERLIN; NVP-LAQ824; INHIBITORS; ANALOGS AB The United States National Cancer Institute (NCI) has been investigating Nature as a source of novel agents for the treatment of cancer for over 45 years, and has contributed to the development of many of the currently available anticancer drugs. The National Cooperative Drug Discovery Group (NCDDG) program was started in 1983 as mechanism to promote multidisciplinary, multi-institutional approaches to drug discovery, and has led to the development of a number of successful clinical agents. The program is reviewed in terms of achievements and challenges facing further research in the exploration of natural resources as a source of new drugs. C1 NCI, Grants & Contracts Operat Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Rockville, MD 20852 USA. NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Rockville, MD 20852 USA. RP Hallock, YF (reprint author), NCI, Grants & Contracts Operat Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, 6130 Execut Blvd,MSC 7456, Rockville, MD 20852 USA. EM hallocky@exchange.nih.gov NR 26 TC 11 Z9 13 U1 0 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2003 VL 41 SU S BP 78 EP 91 DI 10.1080/13880200390517779 PG 14 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 877RK UT WOS:000225587500008 ER PT J AU Altman, RB Flockhart, DA Sherry, ST Oliver, DE Rubin, DL Klein, TE AF Altman, RB Flockhart, DA Sherry, ST Oliver, DE Rubin, DL Klein, TE TI Indexing pharmacogenetic knowledge on the World Wide Web SO PHARMACOGENETICS LA English DT Editorial Material C1 Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Indiana Univ, Div Clin Pharmacol, Indianapolis, IN 46204 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Altman, RB (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA. NR 8 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JAN PY 2003 VL 13 IS 1 BP 3 EP 5 DI 10.1097/00008571-200301000-00002 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 638RL UT WOS:000180584000002 PM 12544507 ER PT J AU Lehrmann, E Oyler, J Vawter, MP Hyde, TM Kolachana, B Kleinman, JE Huestis, ME Becker, KG Freed, WJ AF Lehrmann, E Oyler, J Vawter, MP Hyde, TM Kolachana, B Kleinman, JE Huestis, ME Becker, KG Freed, WJ TI Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse SO PHARMACOGENOMICS JOURNAL LA English DT Article DE addiction; expression patterns; gene profiling; neuroplasticity; psychostimulants ID VENTRAL TEGMENTAL AREA; MESOLIMBIC DOPAMINE SYSTEM; MESSENGER-RNA LEVELS; GENE-EXPRESSION; BEHAVIORAL SENSITIZATION; NEUROFILAMENT PROTEINS; NUCLEUS-ACCUMBENS; MOLECULAR CHARACTERIZATION; MICROARRAY ANALYSIS; DENDRITIC SPINES AB CNS-focused cDNA microarrays were used to examine gene expression profiles in dorsolateral prefrontal cortex (dlPFC, Area 46) from seven individual sets of age- and post-mortem interval-matched male cocaine abusers and controls. The presence of cocaine and related metabolites was confirmed by gas chromatography-mass spectrometry. Sixty-five transcripts were differentially expressed, indicating alterations in energy metabolism, mitochondria and oligodendrocyte function, cytoskeleton and related signaling, and neuronal plasticity. There was evidence for two distinct states of transcriptional regulation, with increases in gene expression predominating in subjects testing positive for a metabolite indicative of recent 'crack' cocaine abuse and decreased expression profiles in the remaining cocaine subjects. This pattern was confirmed by quantitative polymerase chain reaction for select transcripts. These data suggest that cocaine abuse targets a distinct subset of genes in the dlPFC, resulting in either a state of acute activation in which increased gene expression predominates, or a relatively destimulated, refractory phase. C1 NIDA, IRP, NIH, DHHS,Cellular Neurobiol Res Branch, Baltimore, MD 21224 USA. NIDA, Chem & Drug Metab Sect, NIH, DHHS, Baltimore, MD USA. Univ Calif Irvine, Irvine, CA USA. NIMH, Clin Brain Disorders Branch, NIH, DHHS, Bethesda, MD 20892 USA. NIA, DNA Array Unit, Res Resources Branch, NIH,DHHS, Baltimore, MD 21224 USA. RP Lehrmann, E (reprint author), NIDA, IRP, NIH, DHHS,Cellular Neurobiol Res Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656 FU NIDA NIH HHS [Z01 DA000411-08] NR 73 TC 46 Z9 47 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PY 2003 VL 3 IS 1 BP 27 EP 40 DI 10.1038/sj.tpj.6500146 PG 14 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 741HM UT WOS:000186452700008 PM 12629581 ER PT J AU Lin, ZC Uhl, GR AF Lin, ZC Uhl, GR TI Human dopamine transporter gene variation: effects of protein coding variants V55A and V382A on expression and uptake activities SO PHARMACOGENOMICS JOURNAL LA English DT Article DE dopamine transporter (DAT); human variants; dopamine uptake; cocaine affinity; intracellular expression; dominant negative ID DEFICIT HYPERACTIVITY DISORDER; COCAINE ANALOG RECOGNITION; SITE-DIRECTED MUTAGENESIS; PARKINSONS-DISEASE; BIPOLAR DISORDER; MUTANTS; METHYLPHENIDATE; DENSITY; PHOSPHORYLATION; ASSOCIATION AB The human dopamine transporter (DAT, SLC6A3) is an important 15 exon gene for dopamine neurotransmission and dopamine recycling. Common exon 15 variable number tandem repeat variants can be associated with attention deficit/hyperactivity disorder. Rarer single nucleotide polymorphisms produce missense variants including V55A and V382A. We now report studies of the functional influences of these DAT protein-coding variants. In COS cell transient-expression assays, V382A displays about half of the dopamine uptake velocity V-max and cocaine analog binding B-max values of wildtype DAT. V382A lowers dopamine's potency in inhibiting cocaine analog binding by six-fold. Cells expressing V382A or mixtures of V382A and wildtype DAT both display reduced plasma membrane and increased perinuclear expression, consistent with dominant effects of V328A on expression. V55A expresses normally but reveals a 1.7- fold- lower K-m for dopamine uptake. Individuals with these human DAT protein variants could display altered dopamine systems. C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH, Box 5180,Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 19 Z9 19 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PY 2003 VL 3 IS 3 BP 159 EP 168 DI 10.1038/sj.tpj.6500169 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 741QN UT WOS:000186468900005 PM 12815364 ER PT J AU Covitz, PA AF Covitz, PA TI Class struggle: expression profiling and categorizing cancer SO PHARMACOGENOMICS JOURNAL LA English DT Article ID B-CELL LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION; MOLECULAR PORTRAITS; KAPPA-B; MICROARRAY; CLASSIFICATION; CHEMOTHERAPY; PREDICTION; SURVIVAL C1 NCI, Ctr Bioinformat, Rockville, MD 20852 USA. RP Covitz, PA (reprint author), NCI, Ctr Bioinformat, 6116 Execut Blvd,Suite 403, Rockville, MD 20852 USA. EM covitzp@mail.nih.gov NR 27 TC 4 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PY 2003 VL 3 IS 5 BP 257 EP 260 DI 10.1038/sj.tpj.6500187 PG 4 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 741QQ UT WOS:000186469100004 PM 12931128 ER PT J AU Oredipe, OA Furbert-Harris, PM Green, WR White, SL Olden, K Laniyan, I Parish-Gause, D Vaughn, T Griffin, WM Sridhar, R AF Oredipe, OA Furbert-Harris, PM Green, WR White, SL Olden, K Laniyan, I Parish-Gause, D Vaughn, T Griffin, WM Sridhar, R TI Swainsonine stimulates bone marrow cell proliferation and differentiation in different strains of inbred mice SO PHARMACOLOGICAL RESEARCH LA English DT Article DE swainsonine; bone marrow cellularity; colony-forming units ID MURINE; CHEMOTHERAPY; INHIBITION; ADHESION AB The immunomodulatory alkaloid swainsonine (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) has potential for overcoming the bone marrow suppressive effects of cancer chemotherapeutic drugs and radiation. The effect of swainsonine on bone marrow cellularity was evaluated in four different strains (C57BL/6; C3H-HEN; Balb/C and DBA-2 mice) of inbred mice subjected to multiple doses of the alkaloid. Swainsonine treatment stimulated bone marrow cell proliferation in all strains of mice. Examination of the peripheral blood did not reveal any increase in total leukocyte count. In vitro assessment of total colony-forming unit (CFU) capacity of bone marrow cells showed a two- to eight-fold increase in swainsonine treated mice of different strains compared to their corresponding controls given sham injections of physiological saline. Swainsonine induced increase in CFU capacity of bone marrow cells should find clinical application in cancer treatment with chemotherapeutic agents and radiation. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20060 USA. Howard Univ, Coll Med, Dept Pathol, Washington, DC 20060 USA. Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20060 USA. Howard Univ, Coll Med, Dept Radiat Oncol, Washington, DC 20060 USA. Howard Univ, Ctr Canc, Washington, DC 20060 USA. N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Oredipe, OA (reprint author), Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20060 USA. NR 18 TC 16 Z9 22 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD JAN PY 2003 VL 47 IS 1 BP 69 EP 74 AR PII S1043-6618(02)00254-2 DI 10.1016/S1043-6618(02)00254-2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641WG UT WOS:000180769600010 PM 12526864 ER PT J AU Zapata, A Gasior, M Geter-Douglass, B Tortella, FC Newman, AH Witkin, JM AF Zapata, A Gasior, M Geter-Douglass, B Tortella, FC Newman, AH Witkin, JM TI Attenuation of the stimulant and convulsant effects of cocaine by 17-substituted-3-hydroxy and 3-alkoxy derivatives of dextromethorphan SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE sigma-1; NMDA; PCP; dextromethorphan; cocaine; locomotor activity; seizures ID HIGH-AFFINITY DEXTROMETHORPHAN; SIGMA-RECEPTOR LIGANDS; D-ASPARTATE ANTAGONIST; LOCOMOTOR-ACTIVITY; RAT-BRAIN; INDUCED TOXICITY; N-DEMETHYLATION; BINDING-SITES; MICE; PROFILE AB Pharmacological evidence has suggested a role for both sigma and N-methyl-D-aspartate (NMDA) receptors in the behavioral stimulant effects of cocaine and its convulsant effects observed at higher doses. A series of dextromethorphan (DM) analogs with a range of affinities for sigma-1 binding sites and for the NMDA receptor ion channel were used to explore the contribution of these two mechanisms in controlling the stimulant and convulsant effects of cocaine. These compounds were potent and efficacious blockers of both stimulant and convulsant effects produced by acute cocaine administration in mice (cocaine 10 or 75 mg/kg ip, for locomotor activity or convulsions, respectively). Generally, the DM analogs blocked these effects of cocaine at doses that did not display ataxic and sedative side effects as measured in the inverted screen test. In contrast to the high-affinity NMDA blockers, (+)-MK-801 (dizocilpine) and dextrorphan (DX), DM and analogs did not stimulate locomotor activity. There was no significant correlation between the affinities of the DM analogs for the sigma-1 or the phencyclidine (PCP) binding site and their potencies to produce behavioral effects on their own or to attenuate the behavioral or toxic effects of cocaine. The present study has identified a series of agents that have cocaine-blocking effects that appear to be distinct from that of classical sigma-1 receptor ligands and that of traditional uncompetitive NMDA receptor antagonists. These findings point to potentially novel pharmacological strategies for blocking cocaine stimulant and toxic effects. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIDA, Drug Dev Grp, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Walter Reed Army Inst Res, Dept Neuropharmacol & Mol Biol, Div Neurosci, Silver Spring, MD USA. NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Zapata, A (reprint author), NIDA, Drug Dev Grp, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2003 VL 74 IS 2 BP 313 EP 323 AR PII S0091-3057(02)01000-6 DI 10.1016/S0091-3057(02)01000-6 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 633JR UT WOS:000180280600008 PM 12479950 ER PT J AU Chignell, CF Haseman, JK Sik, RH Tennant, RW Trempus, CS AF Chignell, CF Haseman, JK Sik, RH Tennant, RW Trempus, CS TI Photocarcinogenesis in the Tg.AC mouse: Lomefloxacin and 8-methoxypsoralen SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID FLUOROQUINOLONE ANTIBACTERIALS; SKIN TUMORIGENESIS; TRANSGENIC MOUSE; PHOTOTOXICITY; CARCINOGENS; RADIATION AB The Tg.AC mouse is a good predictor of carcinogenic potential when the test article is administered by dorsal painting (Tennant et al. (1995) Environ. Health Perspect. 103, 942). We have used lomefloxacin (LOME) and 8-methoxypsoralen (8-MOP) in combination with UVA to determine whether the Tg.AC transgenic mouse also responds to parenterally administered photocarcinogens. Female Tg.AC mice were given LOME (25 mg/kg intraperitoneal in normal saline) followed by UVA (25 J/cm(2)) 1-2 h later, five times every 2 weeks on a repetitive schedule. Other groups received LOME, UVA or vehicle alone. After 16 weeks, the mean numbers of papillomas/mouse +/- SD (% responding) were: saline, 0.3 +/- 0.5 (33 %); UVA + saline, 1.3 +/- 0.6 (100 %); LOME, 1.9 +/- 1.6 (86%) and LOME-UVA, 1.5 +/- 1.9 (64%). Only the 100% incidence of tumors in the UVA group and the maximum tumor yields in the LOME and UVA groups are significant (P < 0.05) when compared with the control. In a second study, Tg.AC mice were administered the classical photocarcinogen 8-MOP (8 mg/kg intragastric in corn oil) followed by 2 J/cm(2) UVA 1-2 h later, five times every 2 weeks on a repetitive schedule. The second group received 8-MOP, whereas the third was exposed to UVA alone. Papillomas began to appear at 2 weeks in the 8-MOP-UVA group, and after 17 weeks the mean numbers of papillomas/mouse SD (% responding) were: 8-MOP-UVA, 6.9 +/- 8.6 (93%); UVA + corn oil, 1.1 +/- 1.2 (69%) and 8-MOP, 1.1 +/- 1.6 (50%). The maximum tumor yield in the 8-MOP-UVA group was significantly higher (P < 0.01) than that in the other two groups. Our findings suggest that more studies need to be done before the Tg.AC mouse can be used with confidence to identify parenterally administered photocarcinogens. C1 NIEHS, Lab Pharmacol & Chem, ETP, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, EDMP, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis, ETP, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, ETP, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 15 TC 16 Z9 16 U1 1 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN PY 2003 VL 77 IS 1 BP 77 EP 80 DI 10.1562/0031-8655(2003)077<0077:PITTAM>2.0.CO;2 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 637LD UT WOS:000180511800013 PM 12856886 ER PT J AU Huo, YS Winters, WD Yao, DL AF Huo, YS Winters, WD Yao, DL TI Prevention of diet-induced type 2 diabetes in the C57BL/6J mouse model by an antidiabetic herbal formula SO PHYTOTHERAPY RESEARCH LA English DT Article DE herbal formula; diabetes prevention; NIDDM ID PANCREAS AB Significant positive effects of an antidiabetes herbal formula (ADHF) on the prevention of progressive diet-induced type 2 diabetes (NIDDM) in the well recognized C57BL/6J mouse model were demonstrated. The results of the present studies confirm that C57BL/6J mice, through a genetic predisposition, developed NIDDM-like symptoms on a regular schedule when fed solely on a diabetes induction diet containing high fat, high simple carbohydrate and low fibre. Blood glucose levels consistent with type 2 diabetes were detected after 8 weeks on this induction diet. In contrast, no members of the prevention study groups of C57BL/6J mice, which had ADHF mixed into their diabetes induction diet, developed progressive evidence of NIDDM-like symptoms. Specific parameters observed to be significantly reduced in mice in the prevention diet groups fed ADHF mixed into the diabetes induction diet compared with the diabetes positive control groups fed diabetes induction diet only were clinical signs, blood glucose and serum insulin levels, insulin resistance and histopathological changes in major organs. This is the first report to our knowledge to show in vivo evidence for the successful prevention of progressive NIDDM-like symptoms by the addition of an anti-diabetes herbal formula to a effective diabetes induction diet. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78229 USA. NINDS, Expt Neuropathol Lab, NIH, Bethesda, MD 20892 USA. RP Winters, WD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Microbiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 23 TC 6 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD JAN PY 2003 VL 17 IS 1 BP 48 EP 55 DI 10.1002/ptr.1078 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 643MC UT WOS:000180864200008 PM 12557247 ER PT J AU Fins, JJ Bacchetta, MD Miller, FG AF Fins, Joseph J. Bacchetta, Matthew D. Miller, Franklin G. BE McGee, G TI Clinical Pragmatism: A Method of Moral Problem Solving SO PRAGMATIC BIOETHICS, 2ND EDITION SE Basic Bioethics LA English DT Article; Book Chapter C1 [Fins, Joseph J.] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. [Fins, Joseph J.] New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA. [Fins, Joseph J.; Miller, Franklin G.] Hastings Ctr, Garrison, NY USA. [Miller, Franklin G.] NIMH, Intramural Res Program, Bethesda, MD USA. [Miller, Franklin G.] Kennedy Inst Eth, Washington, DC USA. [Miller, Franklin G.] NIH, Dept Clin Bioeth, Bethesda, MD USA. RP Fins, JJ (reprint author), Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-13430-9 J9 BASIC BIOETH PY 2003 BP 29 EP + PG 19 WC Medical Ethics SC Medical Ethics GA BSB35 UT WOS:000284058000005 ER PT J AU Shiono, H Ito, Y AF Shiono, H Ito, Y TI Novel method for continuous cell separation by density gradient centrifugation: Evaluation of a miniature separation column SO PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY LA English DT Article DE cell separation; density gradient centrifugation; Percoll; continuous flow seal-less centrifuge; RBCs; WBCs; lymphocyte; monocyte; granulocyte; platelet; bully coat AB A compact bench-top model of the centrifuge enables continuous cell separation based on density differences. The apparatus holds a small separation disk equipped with a circular channel (8mL capacity) separated by a septum. A set of isotonic Percoll media with different densities is continuously introduced at one terminal and collected from the other. Under a centrifugal force field, cell suspension introduced into the proximal portion of the channel results in continuous separation of cells according to their densities. The performance of the apparatus was demonstrated with the separation of human huffy coat containing nucleated cells (>10(8)) among a large population (10(10)) of RBC. The results indicated that the method is capable of separating a large number of nucleated cells, with minimum damage, for a few hours of operation wherein neutrophils are well resolved from lymphocytes. The method may be applied to other types of samples including cord blood, blood from small animals, cultured cells, pancreatic beta cell islets, malaria parasites, sperm cells, etc. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Aichi Med Univ, Dept Physiol, Nagakute, Aichi, Japan. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3334,50 S Dr,MSC 8014, Bethesda, MD 20892 USA. NR 5 TC 8 Z9 9 U1 0 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6068 J9 PREP BIOCHEM BIOTECH JI Prep. Biochem. Biotechnol. PY 2003 VL 33 IS 2 BP 87 EP 100 DI 10.1081/PB-120021434 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 681TX UT WOS:000183052400001 PM 12784880 ER PT B AU Kim, H Neubert, JK Iadarola, MJ San Miguel, A Goldman, D Dionne, RA AF Kim, H Neubert, JK Iadarola, MJ San Miguel, A Goldman, D Dionne, RA BE Dostrovsky, JO Carr, DB Koltzenburg, M TI Genetic influence on pain sensitivity in humans: Evidence of heritability related to single nucleotide polymorphisms in opioid receptor genes SO PROCEEDINGS OF THE 10TH WORLD CONGRESS ON PAIN SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 10th World Congress on Pain CY AUG 17-22, 2002 CL SAN DIEGO, CA SP Allergan Inc, AstraZeneca, Eli Lilly & Co, Endo Pharmaceut Inc, Grunenthal GmbH, Janssen Pharmaceut, Pfizer Inc, Pharmacia Corp, Purdue-Mundipharma-Napp Associated Co ID NOCICEPTION; MEDIATION; MORPHINE; MOUSE C1 NIDCR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), NIDCR, Pain & Neurosensory Mech Branch, NIH, Bldg 10,Room 1N103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 6 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-46-9 J9 PROG PAIN RES MANAG PY 2003 VL 24 BP 513 EP 520 PG 8 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BW84M UT WOS:000183367100042 ER PT B AU Le, SY Chen, JH Maizel, JV AF Le, SY Chen, JH Maizel, JV GP IEEE COMPUTER SOCIETY TI Statistical inference for well-ordered structures in nucleotide sequences SO PROCEEDINGS OF THE 2003 IEEE BIOINFORMATICS CONFERENCE LA English DT Proceedings Paper CT 2nd International Computational Systems Bioinformatics Conference CY AUG 11-14, 2003 CL STANFORD UNIV, STANFORD, CA SP IEEE Comp Soc TC Bioinformat, ACM HO STANFORD UNIV ID RNA SECONDARY STRUCTURE; TRANSLATIONAL REGULATION; NONCODING RNAS; MESSENGER-RNA; MOLECULES AB Distinct, local structures are frequently correlated with functional RNA elements involved in post-transcriptional regulation of gene expression. Discovery of microRNAs (miRNAs) suggests that there are a large class of small non-coding RNAs in eukaryotic genomes. These miRNAs have the potential to form distinct fold-back stem-loop structures. The prediction of those well-ordered folding sequences (WFS) in genomic sequences is very helpful for our understanding of RNA-based gene regulation and the determination of local RNA elements with structure-dependent functions. In this study, we describe a novel method for discovering the local WFS in a nucleotide sequence by Monte Carlo simulation and RNA folding. In the approach the quality of a local WFS is assessed by the energy difference (E-diff) between the optimal structure folded in the local segment and its corresponding optimal, restrained structure where all the previous base pairings formed in the optimal structure are prohibited Distinct WFS can be discovered by scanning successive segments along a sequence for evaluating the difference between Ediff of the natural sequence and those computed from randomly shuffled sequences. Our results indicate that the statistically significant WFS detected in the genomic sequences of Caenorhabditis elegans (C.elegans) F49E12, T07C5, T07D1, T10H9, Y56A3A and Y71G12B are coincident with known fold-back stem-loops found in miRNA precursors. The potential and implications of our method in searching for miRNAs in genomes is discussed. C1 NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Le, SY (reprint author), NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Bldg 469,Room 151, Frederick, MD 21702 USA. NR 20 TC 3 Z9 3 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2000-6 PY 2003 BP 190 EP 196 DI 10.1109/CSB.2003.1227318 PG 7 WC Biology; Biotechnology & Applied Microbiology; Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Computer Science GA BY34W UT WOS:000188997700032 ER PT B AU VanBuren, V Yoshikawa, T Hamatani, T Ko, MSH AF VanBuren, V Yoshikawa, T Hamatani, T Ko, MSH GP IEEE COMPUTER SOCIETY TI Probe design for large-scale molecular biology applications SO PROCEEDINGS OF THE 2003 IEEE BIOINFORMATICS CONFERENCE LA English DT Proceedings Paper CT 2nd International Computational Systems Bioinformatics Conference CY AUG 11-14, 2003 CL STANFORD UNIV, STANFORD, CA SP IEEE Comp Soc TC Bioinformat, ACM HO STANFORD UNIV AB Large-scale molecular biology technologies such as DNA microarrays and large-scale in situ hybridization (ISH) are used to gain an appreciation of global attributes in biological tissues and cells. Although many of these efforts use cDNA probes, an approach that makes use of designed oligo probes should offer improved consistency at uniform hybridization conditions and improved specificity, as demonstrated by various oligo microarray platforms. We describe a new Web-based application that takes FASTA-formatted sequences as input, and returns both a list of the best choices for probes and a full report containing possible alternatives. Probe design for microarrays may use a scoring routine that optimizes probe intensity based upon an artificial neural network (AAN) trained to predict the average probe intensity from the physical properties of the probe and a screen for possible cross-reactivity. This new tool should provide a reliable way to construct probes that maximize signal intensity while minimizing cross-reactivity. C1 NIA, NIH, Genet Lab, Dev Genom & Aging Sect, Baltimore, MD 21224 USA. RP VanBuren, V (reprint author), NIA, NIH, Genet Lab, Dev Genom & Aging Sect, 333 Cassell Dr,Ste 3000, Baltimore, MD 21224 USA. OI Ko, Minoru/0000-0002-3530-3015 NR 1 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2000-6 PY 2003 BP 502 EP 503 DI 10.1109/CSB.2003.1227388 PG 2 WC Biology; Biotechnology & Applied Microbiology; Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Computer Science GA BY34W UT WOS:000188997700101 ER PT S AU Hassan, M Hattery, D Chernomordik, V Toda, K Fukuhara, K Mittal, D Rowan, J Shah, J Gerber, L Dionne, R Kopin, I Gandjbakhche, AH AF Hassan, M Hattery, D Chernomordik, V Toda, K Fukuhara, K Mittal, D Rowan, J Shah, J Gerber, L Dionne, R Kopin, I Gandjbakhche, AH GP IEEE TI Infrared thermographic imaging for the assessment of temperature asymmetries in reflex sympathetic dystrophy SO PROCEEDINGS OF THE 25TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: A NEW BEGINNING FOR HUMAN HEALTH SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 25th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 17-21, 2003 CL Cancun, MEXICO SP IEEE Engn Med & Biol Soc, Coral, Univ Autonome Metropolitana, Sandia Natl Lab DE reflex sympathetic dystrophy; chronic pain; thermography; Laser Doppler Imaging AB In this on going study, we investigating the usefulness of thermographic patterns as a tool for evaluating reflex sympathetic dystrophy based on results from a clinical trial. Asymmetric thermal patterns and sympathetic responses on the pain side and contra lateral pain-free side after applying cold stimulations are observed. The thermal pattern on the painful side before entry into the drug or placebo treatment is warmer or cooler by at least 1 degreesC and spread over a large area. On the other hand, no remarkable difference is observed between the two sides in LDI blood velocity images. After entry into the drug, thermography shows temperatures on the painful site increase or decrease than the pain-free contra lateral side. In this article we present some cases in which thermography is used to track physiological conditions associated with chronic neuropathic pain. C1 NIH, Bethesda, MD 20892 USA. RP Hassan, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7789-3 J9 P ANN INT IEEE EMBS PY 2003 VL 25 BP 1102 EP 1105 DI 10.1109/IEMBS.2003.1279440 PN 1-4 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BY50W UT WOS:000189395300289 ER PT S AU Martino, RL Kempner, KM Govern, FS Chow, D Steele, ME Elson, JE Coleman, CN AF Martino, RL Kempner, KM Govern, FS Chow, D Steele, ME Elson, JE Coleman, CN GP IEEE TI A collaborative telemedicine environment for the Ireland - Northern Ireland - National cancer institute international partnership in cancer care SO PROCEEDINGS OF THE 25TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: A NEW BEGINNING FOR HUMAN HEALTH SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 25th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 17-21, 2003 CL Cancun, MEXICO SP IEEE Engn Med & Biol Soc, Coral, Univ Autonome Metropolitana, Sandia Natl Lab DE telemedicine; multimedia integration; collaborative technologies; medical imaging AB The Ireland - Northern Ireland - National Cancer Institute Cancer Consortium was established to improve clinical cancer services and patient care on the island of Ireland, and to foster joint collaboration in cancer research and development. An important part of this Consortium was to develop telemedicine systems to facilitate collaboration between participating partners. We have implemented a telemedicine environment for the Consortium based on the TELESYNERGY(R) Medical Consultation WorkStation developed at the U.S. National Institutes of Health. The collaborative use of the system at the three sites has led to the improvement in quality of care in that each patient, regardless of location, can receive an expert assessment and given optimal therapy. The system will be a platform for collaborative clinical and translational research. In the future, this technology will be implemented at additional sites and applied to other medical specialties including cardiology, radiology, and infectious diseases. C1 NIH, Dept Hlth & Human Serv, Ctr Informat Technol, Div Computat Biosci, Bethesda, MD 20892 USA. RP NIH, Dept Hlth & Human Serv, Ctr Informat Technol, Div Computat Biosci, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7789-3 J9 P ANN INT IEEE EMBS PY 2003 VL 25 BP 1350 EP 1353 DI 10.1109/IEMBS.2003.1279549 PN 1-4 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BY50W UT WOS:000189395300353 ER PT S AU Smith, JC Del Negro, CA AF Smith, JC Del Negro, CA GP IEEE TI Nonlinear neural network dynamics in the mammalian respiratory oscillator SO PROCEEDINGS OF THE 25TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: A NEW BEGINNING FOR HUMAN HEALTH SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 25th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 17-21, 2003 CL Cancun, MEXICO SP IEEE Engn Med & Biol Soc, Coral, Univ Autonome Metropolitana, Sandia Natl Lab DE neural oscillator; quasiperiodic dynamics; respiration ID PRE-BOTZINGER COMPLEX; RHYTHM GENERATION; PREBOTZINGER COMPLEX; QUASI-PERIODICITY; PACEMAKER NEURONS; MODELS AB We have analyzed patterns of neural activity in the network responsible for generating respiratory rhythm in mammals. This network produces a limit cycle oscillation in standard conditions in vitro. As network excitability increases the system develops periodic modulation and exhibits mixed-mode oscillations, quasiperiodicity, and disorganized aperiodic activity. We also observed these deterministic breathing patterns during spontaneous breathing in neonatal rodents and human infants in vivo. These results demonstrate that nonlinear network dynamics in the brain can influence rhythmic motor behavior. C1 NINDS, Cellular & Syst Neurobiol Sect, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Smith, JC (reprint author), NINDS, Cellular & Syst Neurobiol Sect, Neural Control Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7789-3 J9 P ANN INT IEEE EMBS PY 2003 VL 25 BP 3816 EP 3818 DI 10.1109/IEMBS.2003.1280993 PN 1-4 PG 3 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BY50W UT WOS:000189395300999 ER PT B AU Rogozin, IB Sorokin, AV Wolf, YI Koonin, EV AF Rogozin, IB Sorokin, AV Wolf, YI Koonin, EV BE Chen, SH Cheng, HD Chiu, DKY Das, S Duro, R Kerre, EE Leong, HV Li, Q Lu, M Romay, MG Ventura, D Wu, J TI Computational pipeline eukaryotic for comparative analysis of gene structure SO PROCEEDINGS OF THE 7TH JOINT CONFERENCE ON INFORMATION SCIENCES LA English DT Proceedings Paper CT 7th Joint Conference on Information Sciences (JCIS) CY SEP 26-30, 2003 CL RES TRIANGLE PK, NC SP Assoc Intelligent Machinery, Duke Univ, Elsevier Publ Inc, Informat Sci Journal, Harbin Inst Technol, NIEHS C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Rogozin, IB (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC INTELLIGENT MACHINERY PI DURHAM PA PO BOX 90291, DURHAM, NC 27708-0291 USA BN 0-9707890-2-5 PY 2003 BP 38 EP 39 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BX96T UT WOS:000187061500011 ER PT B AU Yamanaka, T Toyoshiba, H Portier, CJ AF Yamanaka, T Toyoshiba, H Portier, CJ BE Chen, SH Cheng, HD Chiu, DKY Das, S Duro, R Kerre, EE Leong, HV Li, Q Lu, M Romay, MG Ventura, D Wu, J TI Quantifying gene expression networks: Identifying network structure SO PROCEEDINGS OF THE 7TH JOINT CONFERENCE ON INFORMATION SCIENCES LA English DT Proceedings Paper CT 7th Joint Conference on Information Sciences (JCIS) CY SEP 26-30, 2003 CL RES TRIANGLE PK, NC SP Assoc Intelligent Machinery, Duke Univ, Elsevier Publ Inc, Informat Sci Journal, Harbin Inst Technol, NIEHS DE gene regulatory network; Bayesian network; Bayesian model selection C1 NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. RP Yamanaka, T (reprint author), NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC INTELLIGENT MACHINERY PI DURHAM PA PO BOX 90291, DURHAM, NC 27708-0291 USA BN 0-9707890-2-5 PY 2003 BP 891 EP 892 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BX96T UT WOS:000187061500219 ER PT B AU Parham, F Toyoshiba, H Yamanaka, T Portier, C AF Parham, F Toyoshiba, H Yamanaka, T Portier, C BE Chen, SH Cheng, HD Chiu, DKY Das, S Duro, R Kerre, EE Leong, HV Li, Q Lu, M Romay, MG Ventura, D Wu, J TI A GUI-based program for analysis of DNA microarray data using Bayesian networks SO PROCEEDINGS OF THE 7TH JOINT CONFERENCE ON INFORMATION SCIENCES LA English DT Proceedings Paper CT 7th Joint Conference on Information Sciences (JCIS) CY SEP 26-30, 2003 CL RES TRIANGLE PK, NC SP Assoc Intelligent Machinery, Duke Univ, Elsevier Publ Inc, Informat Sci Journal, Harbin Inst Technol, NIEHS DE DNA microarray; GUI; Bayesian network C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Parham, F (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233,MD A3-06, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC INTELLIGENT MACHINERY PI DURHAM PA PO BOX 90291, DURHAM, NC 27708-0291 USA BN 0-9707890-2-5 PY 2003 BP 893 EP 894 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BX96T UT WOS:000187061500220 ER PT B AU Le, SY Maizel, JV Zhang, KH AF Le, SY Maizel, JV Zhang, KH BE Chen, SH Cheng, HD Chiu, DKY Das, S Duro, R Kerre, EE Leong, HV Li, Q Lu, M Romay, MG Ventura, D Wu, J TI Predicting distinct fold-back structures and related microRNAs in genomic sequences SO PROCEEDINGS OF THE 7TH JOINT CONFERENCE ON INFORMATION SCIENCES LA English DT Proceedings Paper CT 7th Joint Conference on Information Sciences (JCIS) CY SEP 26-30, 2003 CL RES TRIANGLE PK, NC SP Assoc Intelligent Machinery, Duke Univ, Elsevier Publ Inc, Informat Sci Journal, Harbin Inst Technol, NIEHS ID NONCODING RNAS; SYSTEM; GENES AB The discovery of microRNAs (miRNAs) suggests that there is a large class of small non-coding RNAs (ncRNAs) in the genome of Caenorhabditis elegans (C.eleg) and other higher organisms. These miRNAs are a new class of ncRNAs having the potential to pair with nearby nucleotide sequences to form distinct fold-back stem-loops. The prediction of those well-ordered folding sequences (WFS) in genomic sequences is very helpful for the understanding of RNA-based gene regulation. In this study we proposed a new method for discovering the distinct WFS in genomes. In the approach, the quality of local WFS is assessed by the energy difference between the optimal structure folded in the segment and its corresponding constrained optimal structure where all the base pairings form the optimal structure are prohibited. The homologous morphology of fold-back stem-loops is determined by computing structural similarity between two structures. In practice, we first search for those distinct WFS with high statistical significance by scanning successive segments along a genomic sequence. From those detected WFS patterns, we then search for distinct stem-loop structure that are highly similar to the structure morphologies of the known miRNAs. The potential and implications of our discoveries of those distinct WFS with the homologous morphology will be discussed. C1 NCI, Lab Exp & Comp Biol, NIH, Frederick, MD 21702 USA. RP Le, SY (reprint author), NCI, Lab Exp & Comp Biol, NIH, Bldg 469,Room 151, Frederick, MD 21702 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU ASSOC INTELLIGENT MACHINERY PI DURHAM PA PO BOX 90291, DURHAM, NC 27708-0291 USA BN 0-9707890-2-5 PY 2003 BP 933 EP 937 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BX96T UT WOS:000187061500232 ER PT B AU Malyguine, A Shafer-Weaver, K Derby, E Burkett, M Sayers, T Baseler, M AF Malyguine, A Shafer-Weaver, K Derby, E Burkett, M Sayers, T Baseler, M BE ONeill, L TI Granzyme B and IFN-gamma release by effector cells in cell-mediated cytotoxicity SO PROCEEDINGS OF THE INTERNATIONAL CYTOKINE SOCIETY ANNUAL MEETING LA English DT Proceedings Paper CT Annual Meeting of the International-Cytokine-Society CY SEP 20-24, 2003 CL Trinity Coll, Dublin, IRELAND SP Int Cytokine Soc HO Trinity Coll AB Using a Granzyme B (GrB) ELISPOT assay we were able to detect GrB release by CTL upon their contact with relevant target cells. When the GrB ELISPOT assay was directly compared to the IFN-g ELISPOT assay, excellent correlation between these assays was shown, though significant IFN-gamma secretion was detectable later than GrB secretion. Both ELISPOT assays have shown good correlation with 51 Cr release assay, but were significantly faster and more sensitive. Using flow cytometry we demonstrated rapid transfer of GrB from effectors into target cells and phoshatidylserine redistribution on the target cell membrane. Both events were perforin dependent. The data presented suggest that target cell. recognition can trigger rapid release of both GrB and IFN-gamma by CTL. C1 NCI, SAIC Frederick Inc, Lab Cell Mediated Immun, Frederick, MD 21701 USA. RP Malyguine, A (reprint author), NCI, SAIC Frederick Inc, Lab Cell Mediated Immun, Frederick, MD 21701 USA. RI Sayers, Thomas/G-4859-2015 NR 5 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-013-6 PY 2003 BP 105 EP 110 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA BY67X UT WOS:000189437000021 ER PT S AU Antani, S Long, LR Thoma, GR Stanley, RJ AF Antani, S Long, LR Thoma, GR Stanley, RJ GP IEEE IEEE TI Vertebra shape classification using MLP for content-based image retrieval SO PROCEEDINGS OF THE INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS 2003, VOLS 1-4 SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks CY JUL 20-24, 2003 CL PORTLAND, OR SP Int Neural Network Soc, IEEE Neural Networks Soc ID FRACTURES AB A desirable content-based image retrieval (CBIR) system would classify extracted image features to support some form of semantic retrieval. The Lister Hill National Center for Biomedical Communications, an intramural R&D division of the National Library of Medicine (NLM), maintains an archive of digitized x-rays of the cervical and lumbar spine taken as part of the second National Health and Nutrition Examination Survey (NHANES II). It is our goal to provide shape-based access to the digitized x-rays including retrieval on automatically detected and classified pathology, e.g., anterior osteophytes. This is done using radius of curvature analysis along the anterior portion, and morphological analysis for quantifying protrusion regions along the vertebra boundary. Experimental results are presented for the classification of 704 cervical spine vertebrae by evaluating the features using a multi-layer perceptron (MLP) based approach. In this paper, we describe the design and current status of the content-based image retrieval (CBIR) system and the role of neural networks in the design of an effective multimedia information retrieval system. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Commun Engn Branch, Bethesda, MD 20894 USA. RP Antani, S (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Commun Engn Branch, 8600 Rockville Pike, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 15 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1098-7576 BN 0-7803-7898-9 J9 IEEE IJCNN PY 2003 BP 160 EP 165 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA BX30P UT WOS:000184903300031 ER PT B AU Missirlis, F Phillips, JP Jackle, H Rouault, TA AF Missirlis, F Phillips, JP Jackle, H Rouault, TA BE Galaris, D TI Drosophila and antioxidant therapy design SO PROCEEDINGS OF THE MEETING OF THE SOCIETY FOR FREE RADICAL RESEARCH, EUROPEAN SECTION: FREE RADICALS AND OXIDATIVE STRESS: CHEMISTRY, BIOCHEMISTRY AND PATHOPHYSIOLOGICAL IMPLICATIONS LA English DT Proceedings Paper CT Meeting of the Society-for-Free-Radical-Research - Europe CY JUN 26-29, 2003 CL Ioannina, GREECE SP Soc Free Rad Res, European Sect ID OXIDATIVE STRESS; DISEASE; REDUCTASE; MELANOGASTER; MECHANISMS; LONGEVITY; PARAQUAT; SYSTEM; INJURY; CANCER AB Antioxidant intervention is a potential therapeutic approach to mitigate the oxidative stress component of various human diseases. Genetic studies in the model organism Drosophila melanogaster indicate that the major antioxidant defense systems protect from oxidative stress in a compartment-specific manner. They also suggest that compensation for the loss of an antioxidant enzyme by experimentally inducing expression of a second, distinct defense enzyme is possible in a few cases. However, in other examples, overexpression of an antioxidant enzyme may also exacerbate an oxidant-sensitive phenotype. Thus, a successful antioxidant therapy should target the affected tissues, act in the appropriate sub-cellular compartments and specifically rectify the underlying molecular imbalances. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Missirlis, F (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RI Missirlis, Fanis/C-1137-2011 OI Missirlis, Fanis/0000-0003-0467-8444 NR 24 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-002-0 PY 2003 BP 147 EP 151 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY68H UT WOS:000189438000025 ER PT B AU Reines, BP AF Reines, BP BE Linkesch, W TI Seeing aplastic anemia as a natural experiment in anticancer immunity SO PROCEEDINGS OF THE XVII MEETING INTERNATIONAL SOCIETY OF HAEMATOLOGY (EUROPEAN AND AFRICAN DIVISION) LA English DT Proceedings Paper CT 17th European and African Division Meeting of the International-Society-of-Haematology CY SEP 07-10, 2003 CL GRAZ, AUSTRIA SP Int Soc Haematol, European & African Div ID CANCER; FUSION; CELLS C1 NIAID, Cellular & Mol Immunol Lab, T Cell Tolerance Sect, NIH, Bethesda, MD 20892 USA. RP Reines, BP (reprint author), NIAID, Cellular & Mol Immunol Lab, T Cell Tolerance Sect, NIH, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-3147-0 PY 2003 BP 69 EP 72 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA BY21V UT WOS:000188281400011 ER PT J AU Blackshear, PJ Phillips, RS Vazquez-Matias, J Mohrenweiser, H AF Blackshear, PJ Phillips, RS Vazquez-Matias, J Mohrenweiser, H TI Polymorphisms in the genes encoding members of the tristetraprolin family of human tandem CCCH zinc finger proteins SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 75 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review ID ENVIRONMENTAL GENOME PROJECT; EARLY RESPONSE GENE; AU-RICH ELEMENTS; MESSENGER-RNA; TNF-ALPHA; SEQUENCE; CELLS; DEFICIENCY; RECEPTOR; DESTABILIZATION C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med & Biochem, Durham, NC 27710 USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94551 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, A2-05 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES-8054-05] NR 33 TC 16 Z9 17 U1 3 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 J9 PROG NUCLEIC ACID RE PY 2003 VL 75 BP 43 EP 68 DI 10.1016/S0079-6603(03)75002-8 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX76W UT WOS:000186348700002 PM 14604009 ER PT J AU Gallardo-Williams, MT Maronpot, RR Wine, RN Brunssen, SH Chapin, RE AF Gallardo-Williams, MT Maronpot, RR Wine, RN Brunssen, SH Chapin, RE TI Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid SO PROSTATE LA English DT Article DE prostate cancer; boron; enzyme inhibition; serine protease ID NEUTRON-CAPTURE THERAPY; BINDING PROTEIN-3 PROTEASE; SUBTILISIN CARLSBERG; DIETARY BORON; PSA; BOROCAPTATE; ANIMALS; SODIUM; TUMORS; HUMANS AB BACKGROUND. Prostate specific antigen (PSA) is a well-established marker of prostate cancer, but it can also degrade extracellular matrix proteins such as fibronectin and could be involved in tumor progression and metastasis, In this study, we have addressed the use of boric acid and 3-nitrophenyl boronic acid (NPBA) as PSA inhibitors in vitro. METHODS. The inhibition of PSA by boric acid was studied by using specific fluorogenic substrates. Fibronectin, a biologically relevant substrate for PSA, was used as a substrate in a zymographic assay, and the degradation of fibronectin by PSA in the presence of boric acid and NPBA was followed by Western Blot. RESULTS. Low concentrations of boric acid partially inhibited the proteolytic activity of PSA toward a synthetic fluorogenic substrate. Also, by Western blot, we have found significant inhibition in the proteolysis of fibronectin by PSA in the presence of boric acid as well as NPBA. Results indicate that the boronated compounds used in this study can be used for the modulation of PSA activity. CONCLUSION. PSA activity is inhibited in vitro by boric acid and NPBA, If degradation of fibronectin by PSA were, in fact, an important step in the progression of prostate cancer, then borate-induced inhibition of PSA activity should help reduce the development and proliferation of prostate carcinomas. (C) 2002 Wiley-Liss, Inc. C1 Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Gallardo-Williams, MT (reprint author), Natl Inst Environm Hlth Sci, Mol Toxicol Lab, POB 12233 MD E1-06, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 34 TC 33 Z9 35 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JAN 1 PY 2003 VL 54 IS 1 BP 44 EP 49 DI 10.1002/pros.10166 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 631WN UT WOS:000180190300006 PM 12481254 ER PT J AU Elliot, SJ Zorn, BH Mcleod, DG Moul, JW Nyberg, L Striker, LJ Striker, GE AF Elliot, SJ Zorn, BH Mcleod, DG Moul, JW Nyberg, L Striker, LJ Striker, GE TI Pentosan polysulfate decreases prostate smooth muscle proliferation and extracellular matrix turnover SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE benign prostatic hyperplasia; extracellular matrix; tissue inhibitor of MMP; pentosan polysulfate; matrix metalloprotemases (MMP) ID HYPERPLASIA; CELLS; FINASTERIDE AB Benign prostatic hyperplasia (BPH) involves proliferation of smooth muscle cells and increased deposition of extracellular matrix (ECM). We recently found that pentosan polysulfate (PPS) has marked effects on growth and ECM of smooth muscle cells derived from vascular tissues. We examined smooth muscle cells cultured from human prostates and the effects of PPS on their growth and ECM production. Fragments of surgical prostatectomy specimens were diced, digested with collagenase (0.01%), and placed in culture medium supplemented with 20% fetal bovine serum. Outgrowths of elongated cells were characterized by light microscopic examination and immunohistochemical techniques by the presence of F-actin, a-smooth muscle actin, and myosin, which is a characteristic of smooth muscle cells. Two independent isolates were propagated, and growth curves and ECM production were assessed in the presence and absence of PPS (10 or 100 mg/ml). PPS decreased cell number beginning at day 1 and throughout the incubation period, up to 4 days. The amount of the ECM degradative enzymes, metalloproteinases MMP-9 and MMP-2, was examined by zymography. PPS did not alter the amount of MMP-2 in the supernatants but MMP-9 was increased 234.4 +/- 17.23-fold over control cells. Tissue inhibitor of MMP (TIMPS), examined by reverse zymography, increased 200% over control. The amount of alphaI type (IV) and aI type (I) collagen released in the supernatant, measured by ELISA, significantly decreased in PPS-treated cultures. In conclusion, we found that the administration of PPS decreased proliferation as well as ECM production in prostate smooth muscle. Since smooth muscle proliferation and ECM are involved in the pathophysiology of BPH, PPS may have therapeutic potential. C1 Univ Miami, Sch Med, Dept Med, Vasc Biol Inst, Miami, FL 33101 USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Urol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD USA. RP Striker, GE (reprint author), Univ Miami, Sch Med, Dept Med, Vasc Biol Inst, POB 019132 R104, Miami, FL 33101 USA. NR 15 TC 3 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PY 2003 VL 6 IS 2 BP 138 EP 142 DI 10.1038/sj.pcan.4500632 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 693PY UT WOS:000183728600007 PM 12806372 ER PT J AU Wang, W AF Wang, W TI The SWI/SNF family of ATP-Dependent chromatin remodelers: Similar mechanisms for diverse functions SO PROTEIN COMPLEXES THAT MODIFY CHROMATIN SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID SWI-SNF COMPLEX; CELL-CYCLE ARREST; ACTIN-RELATED PROTEIN; SACCHAROMYCES-CEREVISIAE; DNA-BINDING; DROSOPHILA-MELANOGASTER; GENE-EXPRESSION; NUCLEOSOMAL DNA; TRANSCRIPTIONAL ACTIVATION; GLUCOCORTICOID RECEPTOR AB The SWI/SNF family of complexes utilizes the energy of ATP hydrolysis to remodel chromatin structures, thereby allowing transcription factors to gain access to DNA. Recent studies suggest that these remodelers also participate in other DNA metabolic reactions such as replication and viral integration, and even in control of cell growth and tumor suppression. The SWI/SNF remodelers can be classified into at least two distinct subfamilies: one includes human BAF (also known as hSWI/SNF-A) and yeast SWI/SNF; the other comprises human PBAF (hSWI/SNF-B) and yeast RSC. Although both types of complexes have similar subunit composition and chromatin remodeling activity in vitro, they cannot replace each other during transcription mediated by specific activators. Thus, each remodeler probably works with a specific set of activators during gene activation. The availability of distinct types of remodelers can allow cells to regulate expression of a specific group of genes by modulating the activity of corresponding remodelers. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Wang, W (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,TRIAD Ctr Room 4000, Baltimore, MD 21224 USA. NR 120 TC 69 Z9 71 U1 1 U2 7 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2003 VL 274 BP 143 EP 169 PG 27 WC Immunology; Microbiology SC Immunology; Microbiology GA BW29C UT WOS:000181449100006 PM 12596907 ER PT J AU Jones, PL Shi, YB AF Jones, PL Shi, YB TI N-CoR-HDAC corepressor complexes: Roles in transcriptional regulation by nuclear hormone receptors SO PROTEIN COMPLEXES THAT MODIFY CHROMATIN SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID NONHISTONE CHROMOSOMAL PROTEIN; HISTONE DEACETYLASE COMPLEX; MAMMARY-TUMOR VIRUS; RNA POLYMERASE-II; THYROID-HORMONE; XENOPUS-LAEVIS; IN-VIVO; CHROMATIN STRUCTURE; RETINOIC ACID; MEDIATED REPRESSION AB Many nuclear hormone receptors (NHRs) actively repress the expression of their primary response genes through the recruitment of transcriptional corepressor complexes to regulated promoters. N-CoR and the highly related SMRT were originally isolated and characterized by their ability to interact exclusively with the unliganded forms of NHRs and confer transcriptional repression. Recently, both the N-COR and SMRT corepressors have been found to exist in vivo in multiple, distinct macromolecular complexes. While these corepressor complexes differ in overall composition, a general theme is that they contain histone deacetylase enzymatic activity. Several of these complexes contain additional transcriptional corepressor proteins with functional ties to chromatin structure. Together, these data suggest that modulation of chromatin structure plays a central role in N-CoR mediated transcriptional repression from unliganded NHRs. C1 Univ Illinois, Dept Cell & Struct Biol, Urbana, IL 61801 USA. NICHHD, Unit Mol Morphogenesis, NIH, Bethesda, MD 20892 USA. RP Jones, PL (reprint author), Univ Illinois, Dept Cell & Struct Biol, B107 CLSL,601 S Goodwin Ave, Urbana, IL 61801 USA. NR 99 TC 93 Z9 96 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2003 VL 274 BP 237 EP 268 PG 32 WC Immunology; Microbiology SC Immunology; Microbiology GA BW29C UT WOS:000181449100009 PM 12596910 ER PT J AU Ghosh, MC Wang, XT Li, SP Klee, C AF Ghosh, MC Wang, XT Li, SP Klee, C TI Regulation of calcineurin by oxidative stress SO PROTEIN PHOSPHATASES SE METHODS IN ENZYMOLOGY LA English DT Review ID ACTIVE-SITE; PROTEIN PHOSPHATASE; METAL CENTER; DEPHOSPHORYLATION; IDENTIFICATION; INACTIVATION; COMPLEX; ENZYME; BRAIN; ZN C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Fed Reserve Syst, Board Governors, Washington, DC 20551 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Ghosh, MC (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 28 TC 10 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 366 BP 289 EP 304 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY10D UT WOS:000187630800022 PM 14674256 ER PT J AU Bax, A AF Bax, A TI Weak alignment offers new NMR opportunities to study protein structure and dynamics SO PROTEIN SCIENCE LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; LIQUID-CRYSTALLINE MEDIUM; HIGH-RESOLUTION NMR; ORIENTED PHOSPHOLIPID MICELLES; COMPLETE CROSS-VALIDATION; RIGID-BODY MINIMIZATION; CHEMICAL-SHIFTS; HYDROGEN-BONDS; R-FACTOR; PSEUDOCONTACT SHIFTS AB Protein solution nuclear magnetic resonance (NMR) can be conducted in a slightly anisotropic environment, where the orientational distribution of the proteins is no longer random. In such an environment, the large one-bond internuclear dipolar interactions no longer average to zero and report on the average orientation of the corresponding vectors relative to the magnetic field. The desired very weak ordering, on the order of 10(-3), can be induced conveniently by the use of aqueous nematic liquid crystalline suspensions or by anisotropically compressed hydrogels. The resulting residual dipolar interactions are scaled down by three orders of magnitude relative to their static values, but nevertheless can be measured at high accuracy. They are very precise reporters on the average orientation of bonds relative to the molecular alignment frame, and they can be used in a variety of ways to enrich our understanding of protein structure and function. Applications to date have focused primarily on validation of structures, determined by NMR, X-ray crystallography, or homology modeling, and on refinement of structures determined by conventional NMR approaches. Although de novo structure determination on the basis of dipolar couplings suffers from a severe multiple minimum problem, related to the degeneracy of dipolar coupling relative to inversion of the internuclear vector, a number of approaches can address this problem and potentially can accelerate the NMR structure determination process considerably. In favorable cases, where large numbers of dipolar couplings can be measured, inconsistency between measured values can report on internal motions. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 91 TC 290 Z9 296 U1 5 U2 44 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2003 VL 12 IS 1 BP 1 EP 16 DI 10.1110/ps.0233303 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 628FD UT WOS:000179981200001 PM 12493823 ER PT J AU Miyazawa, S Jernigan, RL AF Miyazawa, S Jernigan, RL TI Long- and short-range interactions in native protein structures are consistent/minimally frustrated in sequence space SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE empirical potentials; inverse protein folding; protein folding; protein sequence design; protein sequence-structure compatibility ID STATISTICAL-MECHANICS; CONTACT ENERGIES; DESIGN; RECOGNITION; APPROXIMATION; PACKING; MODELS; FOLD AB We show that long- and short-range interactions in almost all protein native structures are actually consistent with each other for coarse-grained energy scales; specifically we mean the long-range inter-residue contact energies and the short-range secondary structure energies based on peptide dihedral angles, which are potentials of mean force evaluated from residue distributions observed in protein native structures. This consistency is observed at equilibrium in sequence space rather than in conformational. space. Statistical ensembles of sequences are generated by exchanging residues for each of 797 protein native structures with the Metropolis method. It is shown that adding the other category of interaction to either the short- or long-range interactions decreases the means and variances of those energies for essentially all protein native structures, indicating that both interactions consistently work by more-or-less restricting sequence spaces available to one of the interactions. In addition to this consistency, independence by these interaction classes is also indicated by the fact that there are almost no correlations between them when equilibrated using both interactions and significant but small, positive correlations at equilibrium using only one of the interactions. Evidence is provided that protein native sequences can be regarded approximately as samples from the statistical ensembles of sequences with these energy scales and that all proteins have the same effective conformational temperature. Designing protein structures and sequences to be consistent and minimally frustrated among the various interactions is a most effective way to increase protein stability and foldability. C1 Gunma Univ, Fac Technol, Gunma 3768515, Japan. NCI, Lab Expt & Computat Biol, CCR, NIH, Bethesda, MD 20892 USA. Iowa State Univ, Laurence H Baker Ctr Bioinformat & Biol Stat, Inst Plant Sci, Ames, IA USA. RP Miyazawa, S (reprint author), Gunma Univ, Fac Technol, Gunma 3768515, Japan. RI Jernigan, Robert/A-5421-2012 NR 25 TC 15 Z9 16 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JAN 1 PY 2003 VL 50 IS 1 BP 35 EP 43 DI 10.1002/prot.10242 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 630VP UT WOS:000180131100004 PM 12471597 ER PT S AU Morrison, RS Kinoshita, Y Johnson, MD Conrads, TP AF Morrison, RS Kinoshita, Y Johnson, MD Conrads, TP BE Smith, RD Eisenberg, DS Kuriyan, J TI Proteomics in the postgenomic age SO PROTEOME CHARACTERIZATION AND PROTEOMICS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID MAMMARY EPITHELIAL-CELLS; GENE-EXPRESSION PATTERNS; TRAP MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; MOLECULAR CLASSIFICATION; PROTEIN-PHOSPHORYLATION; DILATED CARDIOMYOPATHY; FUNCTIONAL PROTEOMICS; GEL-ELECTROPHORESIS; SUMO-1 MODIFICATION C1 Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Morrison, RS (reprint author), Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. RI Smith, Richard/J-3664-2012 OI Smith, Richard/0000-0002-2381-2349 NR 75 TC 8 Z9 10 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 BN 0-12-034265-0 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2003 VL 65 BP 1 EP 23 PG 23 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX44S UT WOS:000185287400001 PM 12964364 ER PT J AU Zhou, M Yu, LR AF Zhou, M Yu, LR TI Proteomic analysis by two-dimensional polyacrylamide gel electrophoresis SO PROTEOME CHARACTERIZATION AND PROTEOMICS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID IMMOBILIZED PH GRADIENTS; ASSISTED-LASER-DESORPTION/IONIZATION; HELICOBACTER-PYLORI; MASS-SPECTROMETRY; SERUM-PROTEINS; CREATINE-KINASE; ACRYLAMIDE GEL; SYPRO ORANGE; IDENTIFICATION; RESOLUTION C1 NCI, SAIC Frederick, Frederick, MD 21701 USA. RP Zhou, M (reprint author), NCI, SAIC Frederick, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-12400] NR 80 TC 10 Z9 11 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2003 VL 65 BP 57 EP + PG 29 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX44S UT WOS:000185287400003 PM 12964366 ER PT J AU Smith, RD Anderson, GA Lipton, MS Masselon, C Pasa-Tolic, L Udseth, H Belov, M Shen, YF Veenstra, TD AF Smith, RD Anderson, GA Lipton, MS Masselon, C Pasa-Tolic, L Udseth, H Belov, M Shen, YF Veenstra, TD TI High-performance separations and mass spectrometric methods for high-throughput proteomics using accurate mass tags SO PROTEOME CHARACTERIZATION AND PROTEOMICS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID ION-CYCLOTRON RESONANCE; CAPILLARY LIQUID-CHROMATOGRAPHY; COMPLEX PEPTIDE MIXTURES; DEINOCOCCUS-RADIODURANS; ELECTROSPRAY-IONIZATION; PROTEIN IDENTIFICATION; SACCHAROMYCES-CEREVISIAE; HAEMOPHILUS-INFLUENZAE; QUANTITATIVE-ANALYSIS; POLYACRYLAMIDE-GELS C1 Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. RP Smith, RD (reprint author), SAIC Frederick Inc, Biomed Proteom Program, Analyt Chem Lab, NCI, POB B, Ft Detrick, MD 21702 USA. RI Masselon, Christophe/A-2340-2010; Smith, Richard/J-3664-2012 OI Smith, Richard/0000-0002-2381-2349 FU NCI NIH HHS [CA81654]; NCRR NIH HHS [RR12365]; NINDS NIH HHS [NS39617] NR 65 TC 8 Z9 8 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2003 VL 65 BP 85 EP + PG 49 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX44S UT WOS:000185287400004 PM 12964367 ER PT J AU Conrads, TP Issaq, HJ Hoang, VM AF Conrads, TP Issaq, HJ Hoang, VM TI Current strategies for quantitative proteomics SO PROTEOME CHARACTERIZATION AND PROTEOMICS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID PROTEIN IDENTIFICATION TECHNOLOGY; CODED AFFINITY TAGS; 2-DIMENSIONAL ELECTROPHORESIS; GEL-ELECTROPHORESIS; MASS-SPECTROMETRY; PHOSPHORYLATION; PHOSPHATASES; EXPRESSION; COMPONENT; ACCURATE C1 NCI, SAIC Frederick, Biomed Proteom Program, Ft Detrick, MD 21702 USA. RP Conrads, TP (reprint author), NCI, SAIC Frederick, Biomed Proteom Program, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 39 TC 11 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2003 VL 65 BP 133 EP 159 PG 27 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX44S UT WOS:000185287400005 PM 12964368 ER PT J AU Veenstra, TD AF Veenstra, TD TI Proteome analysis of posttranslational modifications SO PROTEOME CHARACTERIZATION AND PROTEOMICS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID ELECTRON-CAPTURE DISSOCIATION; FLIGHT-MASS-SPECTROMETRY; MITOGEN-ACTIVATED PROTEIN; INFRARED MULTIPHOTON DISSOCIATION; SITE-SPECIFIC PHOSPHORYLATION; MULTIPLY-CHARGED IONS; AFFINITY-CHROMATOGRAPHY; KINASE; GLYCOSYLATION; DIGESTION C1 SAIC Frederick Inc, NCI, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), SAIC Frederick Inc, NCI, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 55 TC 7 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2003 VL 65 BP 161 EP 194 PG 34 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX44S UT WOS:000185287400006 PM 12964369 ER PT J AU Issaq, HJ AF Issaq, HJ TI Application of separation technologies to proteomics research SO PROTEOME CHARACTERIZATION AND PROTEOMICS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID CAPILLARY-ZONE-ELECTROPHORESIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; FLIGHT MASS-SPECTROMETRY; GEL-ELECTROPHORESIS; 2-DIMENSIONAL ELECTROPHORESIS; SACCHAROMYCES-CEREVISIAE; AFFINITY-CHROMATOGRAPHY; PROTEIN IDENTIFICATION; PEPTIDES; CELL C1 NCI, SAIC Frederick, Analyt Chem Lab, Separat Technol Grp, Ft Detrick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick, Analyt Chem Lab, Separat Technol Grp, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 57 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2003 VL 65 BP 249 EP 269 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX44S UT WOS:000185287400009 PM 12964372 ER PT S AU Horwitz, B Husain, FT Tagamets, MA AF Horwitz, B Husain, FT Tagamets, MA BE Ng, V Barker, GJ Hendler, T TI Connectionist approach in functional imaging SO PSYCHIATRIC NEUROIMAGING SE NATO SCIENCE SERIES, SUB-SERIES I: LIFE AND BEHAVIOURAL SCIENCES LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Psychiatric Neuroimaging CY SEP 29-OCT 01, 2002 CL Chiavari, ITALY ID WORKING-MEMORY; DEVELOPMENTAL DYSLEXIA; ANGULAR GYRUS; MODEL; BRAIN; SCHIZOPHRENIA; CORTEX; PET; CONNECTIVITY; ATTENTION AB Understanding human cognition, and its disorders, requires determining how networks of interacting brain regions (i.e., neural networks) are formed, how they function during specific cognitive tasks, and how they are disrupted in neurological and psychiatric disorders. Besides ascertaining which brain regions constitute the important nodes of a network mediating a specific cognitive function, it is also crucial to determine the strengths of the connections between these nodes. Functional neuroimaging provides data that can be used to delineate these networks and their connectivity. This chapter discusses three aspects of the connectionist approach to functional brain imaging: (1) how functional connectivity can be used to discover disordered brain circuitry; (2) how the functional strengths of specific neuroanatomical links (i.e., the effective connectivity) in a neural network can be used to evaluate how efficiently (or correctly) a neural system is functioning; and (3) how large-scale neurobiologically realistic network models can be used to help determine the neural substrates mediating human cognitive behavior. C1 NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. RP Horwitz, B (reprint author), NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. NR 29 TC 0 Z9 0 U1 2 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1566-7693 BN 1-58603-344-1 J9 NATO SCI SER I LIFE PY 2003 VL 348 BP 67 EP 72 PG 6 WC Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BBP50 UT WOS:000226885400011 ER PT J AU Dallery, J Houtsmuller, EJ Pickworth, WB Stitzer, ML AF Dallery, J Houtsmuller, EJ Pickworth, WB Stitzer, ML TI Effects of cigarette nicotine content and smoking pace on subsequent craving and smoking SO PSYCHOPHARMACOLOGY LA English DT Article DE rapid smoking; craving; cigarette smokers; sensory cues; nicotine content ID RAPID SMOKING; WITHDRAWAL; ABSTINENCE; EXPOSURE; COCAINE; SATISFACTION; MAINTENANCE; SYMPTOMS; BLOCKADE; RELAPSE AB Rationale: The relative contribution of sensory and pharmacological variables in regulating craving and smoking remains unclear. Rapid smoking procedures and denicotinized cigarettes can be used to further disentangle these factors, and to explore the relationship between craving and smoking. Objective: The present study examined the role of nicotine and sensory cues in mediating craving and smoking, and the relationship between craving and smoking. Methods: Participants (n=15) engaged in one session each of rapid smoking (up to nine cigarettes with puffs taken every 6 s) and normal paced smoking with nicotinized and denicotinized cigarettes (total of four sessions). During the next 3 h, craving and withdrawal assessments and smoking opportunities were scheduled every 15 min. Plasma nicotine levels were measured at baseline, immediately and 15 min after the smoking interventions, and subsequently at the time when the participant first chose to smoke. Results: Craving ratings were equally suppressed immediately after all conditions. After self-paced conditions, both types of cigarettes produced equivalent effects on latency to smoke. Latency to smoke was significantly longer after rapid smoking of nicotinized cigarettes compared to all other conditions. Finally, changes in craving were associated with choices to smoke. Conclusions: The sensory cues associated with smoking suppressed craving ratings regardless of the smoking pace or nicotine content. Only at high doses did nicotine levels play an additional role in acutely suppressing smoking behavior. Small elevations in craving ratings were associated with choices to smoke. C1 Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. NIDA, Div Intramural Res, Bethesda, MD 20892 USA. RP Dallery, J (reprint author), Univ Florida, Dept Psychol, POB 112250, Gainesville, FL 32611 USA. FU NIDA NIH HHS [DA03893, DA131125, T32 DA07209] NR 30 TC 43 Z9 43 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2003 VL 165 IS 2 BP 172 EP 180 DI 10.1007/s00213-002-1242-8 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 644CC UT WOS:000180899500009 PM 12417964 ER PT J AU Duncan, CC Kosmidis, MH Mirsky, AF AF Duncan, CC Kosmidis, MH Mirsky, AF TI Event-related potential assessment of information processing after closed head injury SO PSYCHOPHYSIOLOGY LA English DT Article DE closed head injury; information processing; event-related potentials; N200; P300; reaction time ID TRAUMATIC BRAIN INJURY; AUDITORY ODDBALL TASK; P300 COMPONENT; REACTION-TIME; DISCRIMINATION TASK; CEREBRAL CONCUSSION; COGNITIVE FUNCTION; VISUAL-ATTENTION; DYSFUNCTION; GENERATORS AB We evaluated alterations in information processing after closed head injury as a function of task demands and stimulus modality. Visual and auditory discrimination tasks ere administered to I I survivors of a head injury and 16 matched healthy controls. In auditory tasks. compared with controls the survivors had smaller N100s, smaller and later N200s, a more posterior scalp distribution of N200 and longer P300 and response latencies. Auditors N200 and P300 correlated highly with duration of unconsciousness. In contrast, in visual tasks, only a reduced N200 in the survivors differentiated the groups. Our results indicate that processing of auditory stimuli. including the perception and discrimination Of Stimulus features and the evaluation and categorization of Stimuli, may be impaired after head trauma. Visual sensory processing may be spared but higher-order visual processing involved ill Stimulus classification may be compromised. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Clin Psychophysiol & Psychopharmacol Lab, Bethesda, MD 20814 USA. NIMH, Sect Clin & Expt Neuropsychol, Bethesda, MD 20892 USA. RP Kosmidis, MH (reprint author), MSC 2615,5415 W Cedar Lane,Suite 203B, Bethesda, MD 20892 USA. NR 92 TC 19 Z9 25 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2003 VL 40 IS 1 BP 45 EP 59 DI 10.1111/1469-8986.00006 PG 15 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 636KT UT WOS:000180455300006 PM 12751803 ER PT J AU Blair, RJR Smith, BW Budhani, S Kosson, DS AF Blair, RJR Smith, BW Budhani, S Kosson, DS TI Passive avoidance learning in individuals with psychopathy and its neural substrate SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, IL SP Soc Psychophysiol Res C1 NIMH, Bethesda, MD 20892 USA. UCL, London WC1E 6BT, England. Finch Univ Hlth Sci Chicago Med Sch, N Chicago, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S8 EP S8 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400025 ER PT J AU Fischler, I McKay, M Anderson, K AF Fischler, I McKay, M Anderson, K TI Emotionality of sentences, trait anxiety, and predictive inferences in reading SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res DE anxiety; reading; N400 C1 Univ Florida, NIMH Ctr Study Emot & Attent, Dept Psychol, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S39 EP S39 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400154 ER PT J AU Mata-Martin, JL Ruiz-Padia, E Vila, J Sollers, JJ Thayer, JF AF Mata-Martin, JL Ruiz-Padia, E Vila, J Sollers, JJ Thayer, JF TI Habituation of the cardiac defense response is modulated by heart rate variability SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res DE cardiac defense; heart rate variability; habituation C1 Univ Granada, E-18071 Granada, Spain. Univ Jaen, Jaen, Spain. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S57 EP S58 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400227 ER PT J AU Merritt, MM Sollers, JJ Evans, MK Zonderman, AB Thayer, JF AF Merritt, MM Sollers, JJ Evans, MK Zonderman, AB Thayer, JF TI Depression and autonomic and vascular responses to affective stimuli among older African-American adults SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res DE cardiovascular reactivity; depression; African-Americans C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S59 EP S60 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400235 ER PT J AU Ruiz-Padial, E del Paso, GR Thayer, JF Vila, J AF Ruiz-Padial, E del Paso, GR Thayer, JF Vila, J TI Effects of non-consciously processed emotional pictures on subjective reactivity SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 29-NOV 02, 2003 CL CHICAGO, ILLINOIS SP Soc Psychophysiol Res DE emotion; unconsciousness C1 Univ Jaen, Jaen, Spain. NIA, Bethesda, MD 20892 USA. Univ Granada, E-18071 Granada, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2003 VL 40 SU 1 BP S73 EP S73 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 715BV UT WOS:000184951400289 ER PT J AU Schwartz, AR Gerin, W Davidson, KW Pickering, TG Brosschot, JF Thayer, JF Christenfeld, N Linden, W AF Schwartz, AR Gerin, W Davidson, KW Pickering, TG Brosschot, JF Thayer, JF Christenfeld, N Linden, W TI Toward a causal model of cardiovascular responses to stress and the development of cardiovascular disease SO PSYCHOSOMATIC MEDICINE LA English DT Review DE cardiovascular reactivity; blood pressure; stress; hypertension; coronary artery disease ID HEART-RATE-VARIABILITY; AMBULATORY BLOOD-PRESSURE; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; MENTAL STRESS; ENDOTHELIAL DYSFUNCTION; CAROTID ATHEROSCLEROSIS; ESSENTIAL-HYPERTENSION; LABORATORY REACTIVITY; DEPRESSIVE SYMPTOMS AB Objective: Cardiovascular reactivity is hypothesized to mediate the relationship between stress and cardiovascular disease. We describe three considerations that are crucial for a causal model of cardiovascular responses to stress: the need for laboratory-life generalizability, the role of interactions between environmental exposures and individual response predispositions, and the importance of the duration of both stressor exposure and cardiovascular responding. Methods: We illustrate current understanding of stress-cardiovascular disease relationships with examples from the human and animal psychophysiology, epidemiology, and genetics literature. Results: In a causal model of reactivity, the usefulness of laboratory assessment rests on the assumption that laboratory-based cardiovascular reactivity predicts responses in the natural environment. We find only limited generalizability and suggest that cardiovascular responses to stress can be better understood when examined in the natural environment. The interaction of individual response predispositions and stressor exposures contributes to the development and progression of cardiovascular disease; stress-disease relationships could therefore be better understood if predispositions and exposures were assessed simultaneously in interactive models. Cardiovascular responses to stress are likely to be most deleterious when responses are prolonged. Responses may vary in their magnitude, frequency, and duration; however, reactivity captures only response magnitude. The assessment of anticipatory and recovery measures, with response magnitude, may therefore lead to a more useful model of the stress-disease relationship. Conclusions: A causal model of cardiovascular responses to stress should generalize to the real world, assess interactions between individual predispositions and environmental exposures, and focus on sustained pathogenic exposures and responses. C1 Yale Univ, Sch Med, New Haven, CT USA. Mt Sinai Sch Med, New York, NY USA. Leiden Univ, NL-2300 RA Leiden, Netherlands. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Schwartz, AR (reprint author), 100 York St,Abt 17A, New Haven, CT USA. FU NHLBI NIH HHS [HL47540, HL67677] NR 105 TC 199 Z9 205 U1 6 U2 33 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2003 VL 65 IS 1 BP 22 EP 35 DI 10.1097/01.PSY.0000046075.79922.61 PG 14 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 639BP UT WOS:000180608000004 PM 12554813 ER PT S AU Tronko, MD Bobylyova, OO Bogdanova, TI Epshtein, OV Likhtaryov, IA Markov, VV Oliynyk, VA Tereshchenko, VP Shpak, VM Beebe, G Bouville, A Brill, A Burch, D Fink, D Greenebaum, E Howe, G Luckyanov, N Masnyk, I McConnell, R Robbins, J Thomas, T Voilleque, P AF Tronko, MD Bobylyova, OO Bogdanova, TI Epshtein, OV Likhtaryov, IA Markov, VV Oliynyk, VA Tereshchenko, VP Shpak, VM Beebe, G Bouville, A Brill, A Burch, D Fink, D Greenebaum, E Howe, G Luckyanov, N Masnyk, I McConnell, R Robbins, J Thomas, T Voilleque, P BE Shibata, Y Yamashita, S Watanabe, M Tomonaga, M TI Thyroid gland and radiation - (Ukrainian-American Thyroid Project) SO RADIATION AND HUMANKIND SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 1st Nagasaki Symposium of the International-Consortium-for-Medical-Care-of-Hibakusha-and-Radiation-Lif e-Science CY FEB 21-22, 2003 CL NAGASAKI UNIV SCH MED, POMPE VANMEERDERVOORT HALL, NAGASAKI, JAPAN SP Int Consortium Med Care Hibakusha & Radiat Life Sci HO NAGASAKI UNIV SCH MED, POMPE VANMEERDERVOORT HALL DE Chernobyl; radioiodine; thyroid gland; cancer ID CANCER; CHILDREN AB For the period 1998-2002, in the framework of the Ukraine-USA Thyroid Project, medical screening examinations have been conducted to subjects who were aged 0 to 18 years at the time of the Chernobyl accident. These were residents of eight districts, from Kyiv, Chernihiv, and Zhytomyr regions of the Ukraine, having been most affected following the Chernobyl accident, and having received within several weeks after the accident direct measurements of thyroid doses of gamma radiation. For the period 1998-2000, 13 227 cohort subjects have undergone screening, and in 2001-2002, a repeat screening was performed. As a result of screening, 64 cases of thyroid carcinoma have been identified, including 43 cases after the first screening and 21 cases after the second screening. The distribution of patients by thyroid exposure dose pointed out a predominance of cancer cases in the high-dose group (exposure dose exceeding 1.0 Gy). In addition, 27 cases of benign surgical thyroid pathology have been identified at the first screening, among which were diagnosed 18 cases of follicular adenoma, two cases of multinodular adenomatous goiter, four cases of nodular solitary goiter, one case of fibrous nodule with degenerative changes, one case of diffuse toxic goiter (Graves' disease), and one case of diffuse euthyroid goiter. (C) 2003 Elsevier B.V. All rights reserved. C1 Ukraine Acad Med Sci, Inst Endocrinol & Metab, UA-04114 Kiev, Ukraine. Minist Publ Hlth Ukraine, Kiev, Ukraine. Ukraine Acad Med Sci, Sci Ctr Radiat Med, UA-04114 Kiev, Ukraine. NCI, Rockville, MD USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Columbia Univ, New York, NY USA. NIDDKD, Bethesda, MD 20892 USA. MJP Risk Assessment, Denver, CO USA. RP Tronko, MD (reprint author), Ukraine Acad Med Sci, Inst Endocrinol & Metab, Vyshgorodska Str 69, UA-04114 Kiev, Ukraine. EM endo@i.kiev.ua RI Brill, Aaron/H-3732-2014 OI Brill, Aaron/0000-0001-7538-086X NR 7 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51443-0 J9 INT CONGR SER JI Int. Congr. Ser. PY 2003 VL 1258 BP 91 EP 104 DI 10.1016/S0531-5131(03)01216-0 PG 14 WC Biophysics; Oncology; Genetics & Heredity; Public, Environmental & Occupational Health; Nuclear Science & Technology SC Biophysics; Oncology; Genetics & Heredity; Public, Environmental & Occupational Health; Nuclear Science & Technology GA BY35F UT WOS:000189003800011 ER EF